20-57170017-A-G

Position:

• chr20-57170017-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.*942T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,876 control chromosomes in the GnomAD database, including 15,342 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 0.43 (15342 hom., cov: 31)
  • Exomes 𝑓: 0.56 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: BMP7 NM_001719.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.773

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 = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP7	NM_001719.3	c.*942T>C		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	c.*942T>C		3_prime_UTR_variant	7/7	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65908 AN: 151758 Hom.: 15343 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.431

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.556 AC: 20 AN: 36 Hom.: 4 Cov.: 0 AF XY: 0.500 AC XY: 14 AN XY: 28

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.434 AC: 65917 AN: 151876 Hom.: 15342 Cov.: 31 AF XY: 0.437 AC XY: 32408 AN XY: 74242

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.427

Alfa AF: 0.363 Hom.: 1095

Bravo AF: 0.422

Asia WGS AF: 0.434 AC: 1508 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	0.99
DANN	Benign	0.36

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: rs6025418; hg19: chr20-55745073;