Variant chr20-57183873-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001719.3(BMP7):c.807G>A(p.Gly269=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,614,124 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 12 hom., cov: 33)

Exomes 𝑓: 0.015 ( 187 hom. )

Consequence

BMP7
NM_001719.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.201

Variant links:

Genes affected

BMP7 (HGNC:1074): (bone morphogenetic protein 7) 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, kidney and brown adipose tissue development. Additionally, this protein induces ectopic bone formation and may promote fracture healing in human patients. [provided by RefSeq, Jul 2016]

BMP7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 20-57183873-C-T is Benign according to our data. Variant chr20-57183873-C-T is described in ClinVar as [Benign]. Clinvar id is 2037439.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.201 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0109 (1663/152314) while in subpopulation SAS AF= 0.0222 (107/4828). AF 95% confidence interval is 0.0188. There are 12 homozygotes in gnomad4. There are 797 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1663 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP7	NM_001719.3 linkuse as main transcript	c.807G>A	p.Gly269=	synonymous_variant	4/7	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8 linkuse as main transcript	c.807G>A	p.Gly269=	synonymous_variant	4/7	1	NM_001719.3	ENSP00000379204	P1

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1663

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0224

Gnomad FIN

AF:

0.00659

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0129

AC:

3234

AN:

251274

Hom.:

AF XY:

0.0143

AC XY:

1943

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00879

Gnomad ASJ exome

AF:

0.0210

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0233

Gnomad FIN exome

AF:

0.00857

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.0148

AC:

21580

AN:

1461810

Hom.:

187

Cov.:

AF XY:

0.0152

AC XY:

11084

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00242

Gnomad4 AMR exome

AF:

0.00892

Gnomad4 ASJ exome

AF:

0.0193

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0237

Gnomad4 FIN exome

AF:

0.00877

Gnomad4 NFE exome

AF:

0.0154

Gnomad4 OTH exome

AF:

0.0138

GnomAD4 genome

AF:

0.0109

AC:

1663

AN:

152314

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

797

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.0142

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0222

Gnomad4 FIN

AF:

0.00659

Gnomad4 NFE

AF:

0.0152

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0145

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0183

EpiControl

AF:

0.0165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 21, 2023

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.4

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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