rs61733436

chr20-57183873-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.201

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High AC in GnomAd at 1663 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1663 AN: 152196 Hom.: 12 Cov.: 33

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.: 27 AF XY: 0.0143 AC XY: 1943 AN XY: 135862

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.: 33 AF XY: 0.0152 AC XY: 11084 AN XY: 727212

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.: 12 Cov.: 33 AF XY: 0.0107 AC XY: 797 AN XY: 74476

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.: 30

Bravo AF: 0.0109

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0183

EpiControl AF: 0.0165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs61733436; hg19: chr20-55758929;