rs6025422

chr20-57174725-A-G

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.1035+206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,054 control chromosomes in the GnomAD database, including 21,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (21169 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.724

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=-0.91).
• BP6: Variant 20-57174725-A-G is Benign according to our data. Variant chr20-57174725-A-G is described in ClinVar as [Benign]. Clinvar id is 1258246.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3	c.1035+206T>C		intron_variant		ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.1035+206T>C		intron_variant		1	NM_001719.3	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79418 AN: 151936 Hom.: 21127 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.523 AC: 79528 AN: 152054 Hom.: 21169 Cov.: 33 AF XY: 0.522 AC XY: 38799 AN XY: 74328

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.542

Alfa AF: 0.512 Hom.: 27320

Bravo AF: 0.532

Asia WGS AF: 0.538 AC: 1874 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 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.52

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: rs6025422; hg19: chr20-55749781;