rs6014946

Positions:

• chr20-57169255-A-C
• chr20-57169255-A-G
• chr20-57169255-A-T

Variant summary

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

The NM_001719.3(BMP7):​c.*1704T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,200 control chromosomes in the GnomAD database, including 14,873 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 0.42 (14869 hom., cov: 33)
  • Exomes 𝑓: 0.63 (4 hom.)
• Consequence: BMP7 NM_001719.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP7	NM_001719.3	c.*1704T>G		3_prime_UTR_variant	7/7	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.*1704T>G		3_prime_UTR_variant	7/7	1	NM_001719.3	ENSP00000379204	P1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 64031 AN: 152066 Hom.: 14875 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.625 AC: 10 AN: 16 Hom.: 4 Cov.: 0 AF XY: 0.700 AC XY: 7 AN XY: 10

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.421 AC: 64025 AN: 152184 Hom.: 14869 Cov.: 33 AF XY: 0.424 AC XY: 31563 AN XY: 74392

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.417

Alfa AF: 0.463 Hom.: 2127

Bravo AF: 0.406

Asia WGS AF: 0.433 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.60

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: rs6014946; hg19: chr20-55744311;