chr20-57170429-G-A

Position:

• chr20-57170429-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.*530C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 202,684 control chromosomes in the GnomAD database, including 501 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 0.062 (368 hom., cov: 33)
  • Exomes 𝑓: 0.070 (133 hom.)
• Consequence: BMP7 NM_001719.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3	c.*530C>T		3_prime_UTR_variant	7/7	ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.*530C>T		3_prime_UTR_variant	7/7	1	NM_001719.3	P1

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9382 AN: 152128 Hom.: 368 Cov.: 33

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0382

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.0602

GnomAD4 exome AF: 0.0700 AC: 3532 AN: 50436 Hom.: 133 Cov.: 0 AF XY: 0.0684 AC XY: 1780 AN XY: 26018

Gnomad4 AFR exome AF: 0.0229

Gnomad4 AMR exome AF: 0.0500

Gnomad4 ASJ exome AF: 0.0830

Gnomad4 EAS exome AF: 0.0305

Gnomad4 SAS exome AF: 0.0634

Gnomad4 FIN exome AF: 0.0903

Gnomad4 NFE exome AF: 0.0775

Gnomad4 OTH exome AF: 0.0746

GnomAD4 genome AF: 0.0616 AC: 9381 AN: 152248 Hom.: 368 Cov.: 33 AF XY: 0.0617 AC XY: 4594 AN XY: 74438

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.0452

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0384

Gnomad4 SAS AF: 0.0680

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.0810

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0389 Hom.: 24

Bravo AF: 0.0559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
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: rs17480735; hg19: chr20-55745485;