Variant rs3734444 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_021073.4(BMP5):c.111T>C(p.Ser37=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,613,042 control chromosomes in the GnomAD database, including 149,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.48 ( 18626 hom., cov: 30)

Exomes 𝑓: 0.42 ( 131286 hom. )

Consequence

BMP5
NM_021073.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

BMP5 (HGNC:1072): (bone morphogenetic protein 5) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone and cartilage development. Polymorphisms in this gene may be associated with osteoarthritis in human patients. This gene is differentially regulated in multiple human cancers. This gene encodes distinct protein isoforms that may be similarly proteolytically processed. [provided by RefSeq, Jul 2016]

BMP5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 6-55874755-A-G is Benign according to our data. Variant chr6-55874755-A-G is described in ClinVar as [Benign]. Clinvar id is 3060963.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP5	NM_021073.4 linkuse as main transcript	c.111T>C	p.Ser37=	synonymous_variant	1/7	ENST00000370830.4	NP_066551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP5	ENST00000370830.4 linkuse as main transcript	c.111T>C	p.Ser37=	synonymous_variant	1/7	1	NM_021073.4	ENSP00000359866	P1	P22003-1

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73333

AN:

151610

Hom.:

18593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.643

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.508

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.483

GnomAD3 exomes

AF:

0.433

AC:

108676

AN:

250924

Hom.:

24687

AF XY:

0.426

AC XY:

57787

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.615

Gnomad AMR exome

AF:

0.510

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.169

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.485

Gnomad NFE exome

AF:

0.430

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.419

AC:

611588

AN:

1461316

Hom.:

131286

Cov.:

AF XY:

0.417

AC XY:

302974

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.623

Gnomad4 AMR exome

AF:

0.511

Gnomad4 ASJ exome

AF:

0.488

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.478

Gnomad4 NFE exome

AF:

0.416

Gnomad4 OTH exome

AF:

0.432

GnomAD4 genome

AF:

0.484

AC:

73429

AN:

151726

Hom.:

18626

Cov.:

AF XY:

0.485

AC XY:

35933

AN XY:

74098

show subpopulations

Gnomad4 AFR

AF:

0.608

Gnomad4 AMR

AF:

0.519

Gnomad4 ASJ

AF:

0.495

Gnomad4 EAS

AF:

0.171

Gnomad4 SAS

AF:

0.350

Gnomad4 FIN

AF:

0.508

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.445

Hom.:

27979

Bravo

AF:

0.489

Asia WGS

AF:

0.299

AC:

1040

AN:

3478

EpiCase

AF:

0.437

EpiControl

AF:

0.440

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BMP5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.1

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

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