20-57168747-C-T

Variant names:

• chr20-57168747-C-T
• rs11086598
• NM_001719.3:c.*2212G>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.*2212G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,076 control chromosomes in the GnomAD database, including 15,160 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 (15158 hom., cov: 32)
  • Exomes 𝑓: 0.39 (2 hom.)
• Consequence: BMP7 NM_001719.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 3 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=-0.54).
• 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 rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.*2212G>A		downstream_gene_variant		ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.*2212G>A		downstream_gene_variant		1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65425 AN: 151940 Hom.: 15160 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.389 AC: 7 AN: 18 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 6 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 3 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.430 AC: 65432 AN: 152058 Hom.: 15158 Cov.: 32 AF XY: 0.433 AC XY: 32168 AN XY: 74326

African (AFR) AF: 0.259 AC: 10729 AN: 41482

American (AMR) AF: 0.420 AC: 6420 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1448 AN: 3472

East Asian (EAS) AF: 0.680 AC: 3508 AN: 5162

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4812

European-Finnish (FIN) AF: 0.570 AC: 6023 AN: 10568

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 34092 AN: 67968

Other (OTH) AF: 0.424 AC: 896 AN: 2114

Alfa AF: 0.456 Hom.: 9266

Bravo AF: 0.418

Asia WGS AF: 0.434 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.75
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11086598; hg19: chr20-55743803;