rs6025446

Variant names:

• chr20-57211755-A-G
• rs6025446
• NM_001719.3:c.612-9132T>C

Variant summary

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

The NM_001719.3(BMP7):​c.612-9132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,914 control chromosomes in the GnomAD database, including 17,019 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 0.47 (17019 hom., cov: 32)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.612-9132T>C		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.612-9132T>C		intron_variant	Intron 2 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70844 AN: 151794 Hom.: 17003 Cov.: 32

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.467 AC: 70907 AN: 151914 Hom.: 17019 Cov.: 32 AF XY: 0.465 AC XY: 34528 AN XY: 74246

African (AFR) AF: 0.557 AC: 23075 AN: 41396

American (AMR) AF: 0.493 AC: 7517 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1535 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1684 AN: 5162

South Asian (SAS) AF: 0.541 AC: 2599 AN: 4804

European-Finnish (FIN) AF: 0.396 AC: 4193 AN: 10584

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28831 AN: 67928

Other (OTH) AF: 0.469 AC: 986 AN: 2104

Alfa AF: 0.437 Hom.: 25725

Bravo AF: 0.471

Asia WGS AF: 0.473 AC: 1643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		-0.99
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: rs6025446; hg19: chr20-55786811;