chr20-57217941-G-A

Variant names:

• chr20-57217941-G-A
• rs1475000
• NM_001719.3:c.611+10288C>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+10288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,108 control chromosomes in the GnomAD database, including 34,073 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 (34073 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.611+10288C>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+10288C>T		intron_variant	Intron 2 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100098 AN: 151990 Hom.: 34033 Cov.: 33

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.659 AC: 100200 AN: 152108 Hom.: 34073 Cov.: 33 AF XY: 0.655 AC XY: 48734 AN XY: 74350

African (AFR) AF: 0.834 AC: 34629 AN: 41514

American (AMR) AF: 0.632 AC: 9672 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2089 AN: 3472

East Asian (EAS) AF: 0.366 AC: 1891 AN: 5162

South Asian (SAS) AF: 0.612 AC: 2951 AN: 4818

European-Finnish (FIN) AF: 0.582 AC: 6156 AN: 10578

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.599 AC: 40693 AN: 67958

Other (OTH) AF: 0.651 AC: 1374 AN: 2110

Alfa AF: 0.504 Hom.: 1459

Bravo AF: 0.665

Asia WGS AF: 0.518 AC: 1800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.60
DANN	Benign	0.51
PhyloP100		-1.1
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: rs1475000; hg19: chr20-55792997;