dbSNP rs3734444: BMP5:p.Ser37Ser (chr6-55874755-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_021073.4(BMP5):c.111T>C(p.Ser37Ser) 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

Publications

29 publications found

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 Gene-Disease associations (from GenCC):

dysostosis
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

BMP5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
BMP5	NM_021073.4 link	c.111T>C	p.Ser37Ser	synonymous_variant	Exon 1 of 7	ENST00000370830.4	NP_066551.1	P22003-1M9VUD0A8K694

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP5	ENST00000370830.4 link	c.111T>C	p.Ser37Ser	synonymous_variant	Exon 1 of 7	1	NM_021073.4	ENSP00000359866.3		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

GnomAD2 exomes

AF:

0.433

AC:

108676

AN:

250924

AF XY:

0.426

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 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

African (AFR)

AF:

0.623

AC:

20836

AN:

33426

American (AMR)

AF:

0.511

AC:

22850

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

12756

AN:

26114

East Asian (EAS)

AF:

0.169

AC:

6694

AN:

39686

South Asian (SAS)

AF:

0.363

AC:

31322

AN:

86250

European-Finnish (FIN)

AF:

0.478

AC:

25519

AN:

53414

Middle Eastern (MID)

AF:

0.522

AC:

3009

AN:

5762

European-Non Finnish (NFE)

AF:

0.416

AC:

462512

AN:

1111626

Other (OTH)

AF:

0.432

AC:

26090

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

22840

45679

68519

91358

114198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14116

28232

42348

56464

70580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.484

AC:

73429

AN:

151726

Hom.:

18626

Cov.:

AF XY:

0.485

AC XY:

35933

AN XY:

74098

show subpopulations

African (AFR)

AF:

0.608

AC:

25158

AN:

41384

American (AMR)

AF:

0.519

AC:

7895

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

1715

AN:

3466

East Asian (EAS)

AF:

0.171

AC:

878

AN:

5148

South Asian (SAS)

AF:

0.350

AC:

1682

AN:

4804

European-Finnish (FIN)

AF:

0.508

AC:

5340

AN:

10512

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

28979

AN:

67878

Other (OTH)

AF:

0.488

AC:

1031

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1828

3655

5483

7310

9138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.446

Hom.:

39281

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

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.78

PhyloP100

2.3

Mutation Taster

=86/14

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over