rs6014949

chr20-57177754-A-G

Variant summary

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

The NM_001719.3(BMP7):c.959-2747T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,196 control chromosomes in the GnomAD database, including 22,584 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 0.54 (22584 hom., cov: 35)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3	c.959-2747T>C		intron_variant		ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.959-2747T>C		intron_variant		1	NM_001719.3	P1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81765 AN: 152072 Hom.: 22530 Cov.: 35

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.548

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.538 AC: 81889 AN: 152190 Hom.: 22584 Cov.: 35 AF XY: 0.536 AC XY: 39872 AN XY: 74408

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.552

Alfa AF: 0.512 Hom.: 9308

Bravo AF: 0.551

Asia WGS AF: 0.566 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.1
Dann	Benign	0.72

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: rs6014949; hg19: chr20-55752810;