dbSNP rs80225326: BMP5:p.Gln298Gln (chr6-55774182-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_021073.4(BMP5):c.894A>G(p.Gln298Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00094 in 1,613,070 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 8 hom. )

Consequence

BMP5
NM_021073.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.154

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 6-55774182-T-C is Benign according to our data. Variant chr6-55774182-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3038083.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.154 with no splicing effect.

BS2

High AC in GnomAd4 at 209 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP5	NM_021073.4 link	c.894A>G	p.Gln298Gln	synonymous_variant	Exon 4 of 7	ENST00000370830.4	NP_066551.1	P22003-1M9VUD0A8K694
BMP5	NM_001329754.2 link	c.894A>G	p.Gln298Gln	synonymous_variant	Exon 4 of 6		NP_001316683.1	P22003-2A8K694
BMP5	NM_001329756.2 link	c.894A>G	p.Gln298Gln	synonymous_variant	Exon 4 of 5		NP_001316685.1
BMP5	XM_011514817.4 link	c.894A>G	p.Gln298Gln	synonymous_variant	Exon 4 of 5		XP_011513119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP5	ENST00000370830.4 link	c.894A>G	p.Gln298Gln	synonymous_variant	Exon 4 of 7	1	NM_021073.4	ENSP00000359866.3		P22003-1

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

210

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000825

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00172

AC:

431

AN:

251208

Hom.:

AF XY:

0.00154

AC XY:

209

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0125

Gnomad NFE exome

AF:

0.000907

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000895

AC:

1308

AN:

1461050

Hom.:

Cov.:

AF XY:

0.000903

AC XY:

656

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00402

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.000399

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152020

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

128

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.000810

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000972

Hom.:

Bravo

AF:

0.000332

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BMP5-related disorder

Benign:1

Apr 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

-0.54

CADD

Benign

1.1

DANN

Benign

0.51

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