10-86756838-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_004329.3(BMPR1A):c.-349T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,312 control chromosomes in the GnomAD database, including 7,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7834 hom., cov: 32)
  • Exomes 𝑓: 0.16 (1 hom.)
• Consequence: BMPR1A NM_004329.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.63

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 10-86756838-T-C is Benign according to our data. Variant chr10-86756838-T-C is described in ClinVar as [Benign]. Clinvar id is 301347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1A	NM_004329.3	c.-349T>C		5_prime_UTR_variant	1/13	ENST00000372037.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1A	ENST00000372037.8	c.-349T>C		5_prime_UTR_variant	1/13	1	NM_004329.3	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45118 AN: 151090 Hom.: 7829 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.158 AC: 18 AN: 114 Hom.: 1 Cov.: 0 AF XY: 0.174 AC XY: 15 AN XY: 86

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.299 AC: 45141 AN: 151198 Hom.: 7834 Cov.: 32 AF XY: 0.305 AC XY: 22534 AN XY: 73866

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.299

Alfa AF: 0.315 Hom.: 989

Bravo AF: 0.289

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Generalized juvenile polyposis/juvenile polyposis coli Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	14
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs34755052; hg19: chr10-88516595;