rs6064517

Variant names:

• chr20-57245292-C-T
• rs6064517
• NM_001719.3:c.419-16871G>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.419-16871G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 152,116 control chromosomes in the GnomAD database, including 649 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 0.083 (649 hom., cov: 32)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.419-16871G>A		intron_variant	Intron 1 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.419-16871G>A		intron_variant	Intron 1 of 6	1	NM_001719.3	ENSP00000379204.3
BMP7	ENST00000450594.6	c.419-16871G>A		intron_variant	Intron 1 of 5	2		ENSP00000398687.2
BMP7	ENST00000395864.7	c.419-16871G>A		intron_variant	Intron 1 of 5	5		ENSP00000379205.3
BMP7	ENST00000433911.1	c.74-16871G>A		intron_variant	Intron 1 of 6	5		ENSP00000390814.1

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12570 AN: 151998 Hom.: 648 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0268

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0853

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

GnomAD4 genome AF: 0.0827 AC: 12583 AN: 152116 Hom.: 649 Cov.: 32 AF XY: 0.0828 AC XY: 6154 AN XY: 74362

African (AFR) AF: 0.0421 AC: 1746 AN: 41494

American (AMR) AF: 0.0811 AC: 1239 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0276 AC: 133 AN: 4818

European-Finnish (FIN) AF: 0.122 AC: 1293 AN: 10576

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7491 AN: 67986

Other (OTH) AF: 0.0849 AC: 179 AN: 2108

Alfa AF: 0.0846 Hom.: 104

Bravo AF: 0.0787

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.72
PhyloP100		-1.2
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: rs6064517; hg19: chr20-55820348;