20-57225881-C-T

Position:

• chr20-57225881-C-T

Variant summary

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

The NM_001719.3(BMP7):​c.611+2348G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 469,852 control chromosomes in the GnomAD database, including 38,352 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 0.36 (10532 hom., cov: 32)
  • Exomes 𝑓: 0.41 (27820 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3	c.611+2348G>A		intron_variant		ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.611+2348G>A		intron_variant		1	NM_001719.3	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 53980 AN: 150944 Hom.: 10528 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.361

GnomAD3 exomes AF: 0.375 AC: 56266 AN: 149882 Hom.: 11748 AF XY: 0.385 AC XY: 30991 AN XY: 80584

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.312

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.0267

Gnomad SAS exome AF: 0.439

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.407 AC: 129870 AN: 318788 Hom.: 27820 Cov.: 0 AF XY: 0.413 AC XY: 74394 AN XY: 180126

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.0293

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.437

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.358 AC: 54021 AN: 151064 Hom.: 10532 Cov.: 32 AF XY: 0.361 AC XY: 26650 AN XY: 73850

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.0375

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.357

Alfa AF: 0.382 Hom.: 4829

Bravo AF: 0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.015
DANN	Benign	0.54

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: rs6070031; hg19: chr20-55800937; COSMIC: COSV67782543; COSMIC: COSV67782543;