rs41274738

Variant names:

• chr20-57228243-C-T
• rs41274738
• NM_001719.3:c.597G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

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. 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.42
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• hypospadias

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 20-57228243-C-T is Benign according to our data. Variant chr20-57228243-C-T is described in ClinVar as Benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4128 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.597G>A	p.Gln199Gln	synonymous_variant	Exon 2 of 7	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.597G>A	p.Gln199Gln	synonymous_variant	Exon 2 of 7	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.0272 AC: 4131 AN: 152148 Hom.: 75 Cov.: 32

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

GnomAD2 exomes AF: 0.0288 AC: 7253 AN: 251468 AF XY: 0.0303

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 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.: 32 AF XY: 0.0353 AC XY: 25651 AN XY: 727020

African (AFR) AF: 0.00514 AC: 172 AN: 33462

American (AMR) AF: 0.0171 AC: 767 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0364 AC: 952 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0295 AC: 2547 AN: 86224

European-Finnish (FIN) AF: 0.0307 AC: 1642 AN: 53418

Middle Eastern (MID) AF: 0.0374 AC: 202 AN: 5402

European-Non Finnish (NFE) AF: 0.0389 AC: 43306 AN: 1111990

Other (OTH) AF: 0.0350 AC: 2114 AN: 60360

GnomAD4 genome AF: 0.0271 AC: 4128 AN: 152266 Hom.: 75 Cov.: 32 AF XY: 0.0259 AC XY: 1928 AN XY: 74418

African (AFR) AF: 0.00614 AC: 255 AN: 41552

American (AMR) AF: 0.0236 AC: 361 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0274 AC: 132 AN: 4816

European-Finnish (FIN) AF: 0.0297 AC: 315 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0408 AC: 2775 AN: 68022

Other (OTH) AF: 0.0279 AC: 59 AN: 2116

Alfa AF: 0.0334 Hom.: 53

Bravo AF: 0.0252

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 17003840) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		4.4
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41274738; hg19: chr20-55803299; COSMIC: COSV67780186; COSMIC: COSV67780186;