Variant 6-55759089-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The ENST00000370830.4(BMP5):c.1131C>T(p.Tyr377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000707 in 1,362,090 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00068 ( 10 hom. )

Consequence

BMP5
ENST00000370830.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.14

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=-0.64).

BP6

Variant 6-55759089-G-A is Benign according to our data. Variant chr6-55759089-G-A is described in ClinVar as [Benign]. Clinvar id is 3042737.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000677 (845/1248102) while in subpopulation AMR AF= 0.0183 (702/38360). AF 95% confidence interval is 0.0172. There are 10 homozygotes in gnomad4_exome. There are 342 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BMP5	NM_021073.4 linkuse as main transcript	c.1131C>T	p.Tyr377=	synonymous_variant	6/7	ENST00000370830.4	NP_066551.1
BMP5	NM_001329754.2 linkuse as main transcript	c.1104+1368C>T		intron_variant			NP_001316683.1
BMP5	NM_001329756.2 linkuse as main transcript	c.1028-3407C>T		intron_variant			NP_001316685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP5	ENST00000370830.4 linkuse as main transcript	c.1131C>T	p.Tyr377=	synonymous_variant	6/7	1	NM_021073.4	ENSP00000359866	P1	P22003-1

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

118

AN:

113954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000373

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00266

GnomAD3 exomes

AF:

0.00246

AC:

614

AN:

249464

Hom.:

AF XY:

0.00183

AC XY:

247

AN XY:

135028

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.0168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00279

GnomAD4 exome

AF:

0.000677

AC:

845

AN:

1248102

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

342

AN XY:

618612

show subpopulations

Gnomad4 AFR exome

AF:

0.000219

Gnomad4 AMR exome

AF:

0.0183

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000100

Gnomad4 SAS exome

AF:

0.000107

Gnomad4 FIN exome

AF:

0.0000290

Gnomad4 NFE exome

AF:

0.0000780

Gnomad4 OTH exome

AF:

0.000993

GnomAD4 genome

AF:

0.00104

AC:

118

AN:

113988

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

51946

show subpopulations

Gnomad4 AFR

AF:

0.000372

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00265

Alfa

AF:

0.000519

Hom.:

Asia WGS

AF:

0.00231

AC:

AN:

3468

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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

Jun 27, 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

-0.64

CADD

Benign

9.1

DANN

Benign

0.86

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