rs6123679

chr20-57216292-T-G

Variant summary

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

The NM_001719.3(BMP7):c.611+11937A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 152,254 control chromosomes in the GnomAD database, including 437 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 0.046 (437 hom., cov: 31)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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 (EAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP7	NM_001719.3	c.611+11937A>C		intron_variant		ENST00000395863.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP7	ENST00000395863.8	c.611+11937A>C		intron_variant		1	NM_001719.3	P1

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6922 AN: 152136 Hom.: 430 Cov.: 31

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0428

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0587

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

GnomAD4 genome AF: 0.0455 AC: 6933 AN: 152254 Hom.: 437 Cov.: 31 AF XY: 0.0494 AC XY: 3675 AN XY: 74434

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0428

Gnomad4 NFE AF: 0.0279

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0313 Hom.: 156

Bravo AF: 0.0510

Asia WGS AF: 0.207 AC: 717 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	4.1
Dann	Benign	0.64

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: rs6123679; hg19: chr20-55791348;