rs162315

Positions:

• chr20-57233824-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001719.3(BMP7):​c.419-5403C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,170 control chromosomes in the GnomAD database, including 14,683 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 (14683 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP7	NM_001719.3	c.419-5403C>T		intron_variant		ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.419-5403C>T		intron_variant		1	NM_001719.3	ENSP00000379204	P1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57917 AN: 152052 Hom.: 14661 Cov.: 33

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.381 AC: 58003 AN: 152170 Hom.: 14683 Cov.: 33 AF XY: 0.374 AC XY: 27850 AN XY: 74392

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.371

Alfa AF: 0.279 Hom.: 3719

Bravo AF: 0.412

Asia WGS AF: 0.340 AC: 1182 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	1.9
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs162315; hg19: chr20-55808880;