Variant 20-57228243-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001719.3(BMP7):c.597G>A(p.Gln199Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.0346 in 1,613,682 control chromosomes in the GnomAD database, including 1,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 75 hom., cov: 32)

Exomes 𝑓: 0.035 ( 991 hom. )

Consequence

BMP7
NM_001719.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.42

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:

BMP7 (HGNC:):

BMP7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 20-57228243-C-T is Benign according to our data. Variant chr20-57228243-C-T is described in ClinVar as [Benign]. Clinvar id is 1285787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0271 (4128/152266) while in subpopulation NFE AF= 0.0408 (2775/68022). AF 95% confidence interval is 0.0395. There are 75 homozygotes in gnomad4. There are 1928 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4128 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP7	NM_001719.3 linkuse as main transcript	c.597G>A	p.Gln199Gln	synonymous_variant	2/7	ENST00000395863.8	NP_001710.1	P18075A8K571

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8 linkuse as main transcript	c.597G>A	p.Gln199Gln	synonymous_variant	2/7	1	NM_001719.3	ENSP00000379204.3		P18075

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

4131

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00615

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.0395

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0278

Gnomad FIN

AF:

0.0297

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0408

Gnomad OTH

AF:

0.0282

GnomAD3 exomes

AF:

0.0288

AC:

7253

AN:

251468

Hom.:

125

AF XY:

0.0303

AC XY:

4114

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00541

Gnomad AMR exome

AF:

0.0166

Gnomad ASJ exome

AF:

0.0387

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0293

Gnomad FIN exome

AF:

0.0307

Gnomad NFE exome

AF:

0.0393

Gnomad OTH exome

AF:

0.0270

GnomAD4 exome

AF:

0.0354

AC:

51707

AN:

1461416

Hom.:

991

Cov.:

AF XY:

0.0353

AC XY:

25651

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.00514

Gnomad4 AMR exome

AF:

0.0171

Gnomad4 ASJ exome

AF:

0.0364

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0295

Gnomad4 FIN exome

AF:

0.0307

Gnomad4 NFE exome

AF:

0.0389

Gnomad4 OTH exome

AF:

0.0350

GnomAD4 genome

AF:

0.0271

AC:

4128

AN:

152266

Hom.:

Cov.:

AF XY:

0.0259

AC XY:

1928

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00614

Gnomad4 AMR

AF:

0.0236

Gnomad4 ASJ

AF:

0.0395

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0274

Gnomad4 FIN

AF:

0.0297

Gnomad4 NFE

AF:

0.0408

Gnomad4 OTH

AF:

0.0279

Alfa

AF:

0.0336

Hom.:

Bravo

AF:

0.0252

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 16, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2018	This variant is associated with the following publications: (PMID: 17003840) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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