Variant chr10-86756333-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001406562.1(BMPR1A):c.-373+229G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 152,116 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 348 hom., cov: 32)

Exomes 𝑓: 0.11 ( 0 hom. )

Consequence

BMPR1A
NM_001406562.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.17

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:

ENSG00000272631 (HGNC:):

ENSG00000272631 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 10-86756333-G-C is Benign according to our data. Variant chr10-86756333-G-C is described in ClinVar as [Benign]. Clinvar id is 1277039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-86756333-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
BMPR1A	NM_001406562.1 link	c.-373+229G>C	intron_variant	NP_001393491.1
BMPR1A	NM_001406564.1 link	c.-373+370G>C	intron_variant	NP_001393493.1
BMPR1A	NM_001406566.1 link	c.-268+370G>C	intron_variant	NP_001393495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272631	ENST00000608826.1 link	n.-35C>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0538

AC:

8180

AN:

151978

Hom.:

347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0422

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.000969

Gnomad SAS

AF:

0.0306

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0739

Gnomad OTH

AF:

0.0570

GnomAD4 exome

AF:

0.107

AC:

AN:

Hom.:

Cov.:

AF XY:

0.136

AC XY:

AN XY:

show subpopulations

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.0833

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0538

AC:

8179

AN:

152088

Hom.:

348

Cov.:

AF XY:

0.0552

AC XY:

4106

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.0420

Gnomad4 ASJ

AF:

0.0280

Gnomad4 EAS

AF:

0.000972

Gnomad4 SAS

AF:

0.0300

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.0739

Gnomad4 OTH

AF:

0.0564

Alfa

AF:

0.0318

Hom.:

Bravo

AF:

0.0457

Asia WGS

AF:

0.0340

AC:

120

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.4

DANN

Benign

0.39

Splicing

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