NM_001719.3:c.612-9943C>T

Variant names:

• chr20-57212566-G-A
• rs12481628
• NM_001719.3:c.612-9943C>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.612-9943C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,094 control chromosomes in the GnomAD database, including 19,418 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 0.49 (19418 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.96
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.612-9943C>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.612-9943C>T		intron_variant	Intron 2 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74812 AN: 151976 Hom.: 19413 Cov.: 33

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.492 AC: 74846 AN: 152094 Hom.: 19418 Cov.: 33 AF XY: 0.494 AC XY: 36730 AN XY: 74340

African (AFR) AF: 0.334 AC: 13837 AN: 41488

American (AMR) AF: 0.569 AC: 8713 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1953 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1512 AN: 5178

South Asian (SAS) AF: 0.595 AC: 2871 AN: 4824

European-Finnish (FIN) AF: 0.533 AC: 5620 AN: 10546

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38611 AN: 67976

Other (OTH) AF: 0.533 AC: 1124 AN: 2108

Alfa AF: 0.502 Hom.: 7109

Bravo AF: 0.481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.025
DANN	Benign	0.61
PhyloP100		-4.0
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: rs12481628; hg19: chr20-55787622;