chr20-57216700-G-A

Variant names:

• chr20-57216700-G-A
• rs230205
• NM_001719.3:c.611+11529C>T

Variant summary

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

The NM_001719.3(BMP7):​c.611+11529C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,974 control chromosomes in the GnomAD database, including 33,929 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 0.66 (33929 hom., cov: 32)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.611+11529C>T		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.611+11529C>T		intron_variant	Intron 2 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99820 AN: 151856 Hom.: 33889 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.657 AC: 99922 AN: 151974 Hom.: 33929 Cov.: 32 AF XY: 0.655 AC XY: 48623 AN XY: 74278

African (AFR) AF: 0.833 AC: 34486 AN: 41424

American (AMR) AF: 0.633 AC: 9671 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2097 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1770 AN: 5154

South Asian (SAS) AF: 0.621 AC: 2992 AN: 4820

European-Finnish (FIN) AF: 0.579 AC: 6127 AN: 10588

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40640 AN: 67928

Other (OTH) AF: 0.656 AC: 1385 AN: 2110

Alfa AF: 0.636 Hom.: 4091

Bravo AF: 0.664

Asia WGS AF: 0.521 AC: 1811 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.84
PhyloP100		-0.20
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: rs230205; hg19: chr20-55791756;