rs17404303

Positions:

• chr20-57228631-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001719.3(BMP7):​c.419-210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,032 control chromosomes in the GnomAD database, including 9,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (9169 hom., cov: 32)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-57228631-C-T is Benign according to our data. Variant chr20-57228631-C-T is described in ClinVar as [Benign]. Clinvar id is 667563.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP7	NM_001719.3	c.419-210G>A		intron_variant		ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.419-210G>A		intron_variant		1	NM_001719.3	ENSP00000379204	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48374 AN: 151916 Hom.: 9171 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.333

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.318 AC: 48402 AN: 152032 Hom.: 9169 Cov.: 32 AF XY: 0.324 AC XY: 24037 AN XY: 74292

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.0382

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.330

Alfa AF: 0.405 Hom.: 25669

Bravo AF: 0.293

Asia WGS AF: 0.183 AC: 637 AN: 3478

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

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs17404303; hg19: chr20-55803687;