20-57215091-T-C

Position:

• chr20-57215091-T-C

Variant summary

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

The NM_001719.3(BMP7):​c.612-12468A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,240 control chromosomes in the GnomAD database, including 35,846 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 0.67 (35835 hom., cov: 34)
  • Exomes 𝑓: 0.65 (11 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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]

BMP7-AS1 (HGNC:40096): (BMP7 antisense RNA 1)

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 (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3	c.612-12468A>G		intron_variant		ENST00000395863.8
BMP7-AS1	NR_110631.1	n.653+143T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.612-12468A>G		intron_variant		1	NM_001719.3	P1
BMP7-AS1	ENST00000445956.1	n.77+143T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102424 AN: 152068 Hom.: 35794 Cov.: 34

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.648 AC: 35 AN: 54 Hom.: 11 AF XY: 0.588 AC XY: 20 AN XY: 34

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.650

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.674 AC: 102530 AN: 152186 Hom.: 35835 Cov.: 34 AF XY: 0.670 AC XY: 49869 AN XY: 74410

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.669

Alfa AF: 0.621 Hom.: 38581

Bravo AF: 0.682

Asia WGS AF: 0.536 AC: 1861 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	1.3
DANN	Benign	0.65

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: rs6025447; hg19: chr20-55790147;