rs230188

Variant names:

• chr20-57195460-T-C
• rs230188
• NM_001719.3:c.760+7015A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001719.3(BMP7):​c.760+7015A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,128 control chromosomes in the GnomAD database, including 32,660 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (32660 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.760+7015A>G		intron_variant	Intron 3 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.760+7015A>G		intron_variant	Intron 3 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97525 AN: 152010 Hom.: 32611 Cov.: 33

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.642 AC: 97645 AN: 152128 Hom.: 32660 Cov.: 33 AF XY: 0.640 AC XY: 47611 AN XY: 74374

African (AFR) AF: 0.832 AC: 34530 AN: 41508

American (AMR) AF: 0.637 AC: 9746 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2054 AN: 3468

East Asian (EAS) AF: 0.287 AC: 1482 AN: 5158

South Asian (SAS) AF: 0.620 AC: 2993 AN: 4824

European-Finnish (FIN) AF: 0.542 AC: 5737 AN: 10584

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39094 AN: 67976

Other (OTH) AF: 0.631 AC: 1331 AN: 2110

Alfa AF: 0.592 Hom.: 14940

Bravo AF: 0.651

Asia WGS AF: 0.544 AC: 1893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.56
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs230188; hg19: chr20-55770516;