10-86921701-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004329.3(BMPR1A):c.1342+6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,614,160 control chromosomes in the GnomAD database, including 252 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 131 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 121 hom. )

Consequence

BMPR1A
NM_004329.3 splice_region, intron

Scores

Splicing: ADA: 0.00005585

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:16

Conservation

PhyloP100: 0.154

Variant links:

Genes affected

BMPR1A (HGNC:1076): (bone morphogenetic protein receptor type 1A) The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors, ACVR1 and ACVR2. The ligands of these receptors are members of the TGF-beta superfamily. TGF-betas and activins transduce their signals through the formation of heteromeric complexes with 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding. [provided by RefSeq, Jul 2008]

BMPR1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-86921701-A-G is Benign according to our data. Variant chr10-86921701-A-G is described in ClinVar as [Benign]. Clinvar id is 301352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86921701-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1A	NM_004329.3 link	c.1342+6A>G		splice_region_variant, intron_variant	Intron 11 of 12	ENST00000372037.8	NP_004320.2	P36894

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR1A	ENST00000372037.8 link	c.1342+6A>G		splice_region_variant, intron_variant	Intron 11 of 12	1	NM_004329.3	ENSP00000361107.2		P36894

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

3375

AN:

152192

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0775

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00586

AC:

1474

AN:

251490

Hom.:

AF XY:

0.00442

AC XY:

601

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0812

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00236

AC:

3447

AN:

1461850

Hom.:

121

Cov.:

AF XY:

0.00205

AC XY:

1489

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0855

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000701

Gnomad4 OTH exome

AF:

0.00503

GnomAD4 genome

AF:

0.0222

AC:

3382

AN:

152310

Hom.:

131

Cov.:

AF XY:

0.0211

AC XY:

1572

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0774

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.0261

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:16

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 07, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 23, 2020

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Juvenile polyposis syndrome

Benign:3

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 07, 2024

Myriad Genetics, Inc.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hereditary cancer-predisposing syndrome

Benign:2

Mar 09, 2016

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 20, 2025

Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The splice region variant NM_004329.3(BMPR1A):c.1342+6A>G has been reported to ClinVar as Benign with a status of (2 stars) criteria provided, multiple submitters, no conflicts (Variation ID 301352 as of 2025-01-02).The c.1342+6A>G variant is observed in 130/5,008 (2.5958%) alleles from individuals of 1kG All background in 1kG, indicating it is a common benign variant. The c.1342+6A>G variant is not predicted to disrupt the existing donor splice site 4bp upstream by any splice site algorithm. The c.1342+6A>G variant results in a substitution of a base that is not predicted conserved by GERP++ and PhyloP. For these reasons, this variant has been classified as Benign. -

Polyposis syndrome, hereditary mixed, 2

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

The BMPR1A c.1342+6A>G was identified in dbSNP (ID: rs55763614) as â€šÃ„ÃºWith Likely benign alleleâ€šÃ„Ã¹, and ClinVar (classified as benign by Invitae, Quest Diagnostics Nichols Institute San Juan Capistrano, Color, Prevention Genetics and Mayo Clinic Genetic Testing Laboratories; and likely benign by Illumina). The variant was identified in control databases in 2067 (75 homozygous) of 277240 chromosomes at a frequency of 0.007 (Genome Aggregation Database Feb 27, 2017), observed in the following populations: African in 1906 (75 homozygous) of 24032 chromosomes (freq: 0.08), Other in 18 of 6466 chromosomes (freq: 0.003), Latino in 118 of 34418 chromosomes (freq: 0.003), European Non-Finnish in 22 of 126728 chromosomes (freq: 0.0002), and South Asian in 3 of 30780 chromosomes (freq: 0.0001), while not observed in the Ashkenazi Jewish, East Asian, and European Finnish populations. The c.1342+6A>G variant is located in the 5' splice region but does not affect the invariant +1 and +2 positions. However, positions +3 to +6 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. -

Generalized juvenile polyposis/juvenile polyposis coli

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000056

dbscSNV1_RF

Benign

0.022

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over