rs6127973

chr20-57231224-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001719.3(BMP7):c.419-2803C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,146 control chromosomes in the GnomAD database, including 1,229 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 0.11 (1229 hom., cov: 34)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3	c.419-2803C>T		intron_variant		ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.419-2803C>T		intron_variant		1	NM_001719.3	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17177 AN: 152028 Hom.: 1232 Cov.: 34

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.113 AC: 17174 AN: 152146 Hom.: 1229 Cov.: 34 AF XY: 0.114 AC XY: 8509 AN XY: 74382

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.106

Alfa AF: 0.136 Hom.: 2003

Bravo AF: 0.111

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.84
Dann	Benign	0.66

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: rs6127973; hg19: chr20-55806280;