rs6127980

Variant names:

• chr20-57248706-G-A
• rs6127980
• NM_001719.3:c.418+16999C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-57248706-G-A
• chr20-57248706-G-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.418+16999C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,220 control chromosomes in the GnomAD database, including 2,366 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 0.17 (2366 hom., cov: 32)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.418+16999C>T		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.418+16999C>T		intron_variant	Intron 1 of 6	1	NM_001719.3	ENSP00000379204.3
BMP7	ENST00000450594.6	c.418+16999C>T		intron_variant	Intron 1 of 5	2		ENSP00000398687.2
BMP7	ENST00000395864.7	c.418+16999C>T		intron_variant	Intron 1 of 5	5		ENSP00000379205.3
BMP7	ENST00000433911.1	c.73+16999C>T		intron_variant	Intron 1 of 6	5		ENSP00000390814.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25224 AN: 152102 Hom.: 2363 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.166 AC: 25241 AN: 152220 Hom.: 2366 Cov.: 32 AF XY: 0.164 AC XY: 12181 AN XY: 74424

African (AFR) AF: 0.239 AC: 9926 AN: 41518

American (AMR) AF: 0.231 AC: 3538 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1072 AN: 5182

South Asian (SAS) AF: 0.145 AC: 701 AN: 4828

European-Finnish (FIN) AF: 0.0910 AC: 964 AN: 10598

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8010 AN: 68006

Other (OTH) AF: 0.181 AC: 383 AN: 2114

Alfa AF: 0.111 Hom.: 374

Bravo AF: 0.181

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.43
DANN	Benign	0.69
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: rs6127980; hg19: chr20-55823762;