20-57203952-C-T

Variant names:

• chr20-57203952-C-T
• rs4811823
• NM_001719.3:c.612-1329G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001719.3(BMP7):​c.612-1329G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,146 control chromosomes in the GnomAD database, including 21,185 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 0.52 (21185 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• hypospadias

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.612-1329G>A		intron_variant	Intron 2 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.612-1329G>A		intron_variant	Intron 2 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79602 AN: 152028 Hom.: 21170 Cov.: 33

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.533

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.524 AC: 79673 AN: 152146 Hom.: 21185 Cov.: 33 AF XY: 0.526 AC XY: 39081 AN XY: 74364

African (AFR) AF: 0.528 AC: 21905 AN: 41482

American (AMR) AF: 0.574 AC: 8780 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3466

East Asian (EAS) AF: 0.254 AC: 1316 AN: 5176

South Asian (SAS) AF: 0.607 AC: 2927 AN: 4824

European-Finnish (FIN) AF: 0.497 AC: 5262 AN: 10590

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35830 AN: 67998

Other (OTH) AF: 0.535 AC: 1129 AN: 2112

Alfa AF: 0.523 Hom.: 5237

Bravo AF: 0.524

Asia WGS AF: 0.499 AC: 1735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.96
DANN	Benign	0.73
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4811823; hg19: chr20-55779008;