rs6127983

Variant names:

• chr20-57249419-T-C
• rs6127983
• NM_001719.3:c.418+16286A>G

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+16286A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,822 control chromosomes in the GnomAD database, including 10,950 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 0.38 (10950 hom., cov: 30)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.418+16286A>G		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+16286A>G		intron_variant	Intron 1 of 6	1	NM_001719.3	ENSP00000379204.3
BMP7	ENST00000450594.6	c.418+16286A>G		intron_variant	Intron 1 of 5	2		ENSP00000398687.2
BMP7	ENST00000395864.7	c.418+16286A>G		intron_variant	Intron 1 of 5	5		ENSP00000379205.3
BMP7	ENST00000433911.1	c.73+16286A>G		intron_variant	Intron 1 of 6	5		ENSP00000390814.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57375 AN: 151704 Hom.: 10941 Cov.: 30

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.378 AC: 57409 AN: 151822 Hom.: 10950 Cov.: 30 AF XY: 0.379 AC XY: 28143 AN XY: 74196

African (AFR) AF: 0.415 AC: 17183 AN: 41386

American (AMR) AF: 0.438 AC: 6680 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1120 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1238 AN: 5114

South Asian (SAS) AF: 0.366 AC: 1759 AN: 4800

European-Finnish (FIN) AF: 0.376 AC: 3964 AN: 10556

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24283 AN: 67916

Other (OTH) AF: 0.381 AC: 803 AN: 2110

Alfa AF: 0.363 Hom.: 31835

Bravo AF: 0.383

Asia WGS AF: 0.331 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		-0.40
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: rs6127983; hg19: chr20-55824475;