rs270413

Positions:

• chr6-7749410-T-C

Variant summary

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

The NM_001718.6(BMP6):​c.664+21791T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,134 control chromosomes in the GnomAD database, including 13,419 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 0.40 (13419 hom., cov: 33)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

Genes affected

BMP6 (HGNC:1073): (bone morphogenetic protein 6) 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. This protein regulates a wide range of biological processes including iron homeostasis, fat and bone development, and ovulation. Differential expression of this gene may be associated with progression of breast and prostate cancer. Mutations in this gene may be associated with iron overload 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP6	NM_001718.6	c.664+21791T>C		intron_variant		ENST00000283147.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP6	ENST00000283147.7	c.664+21791T>C		intron_variant		1	NM_001718.6	P1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60905 AN: 152016 Hom.: 13427 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.400 AC: 60902 AN: 152134 Hom.: 13419 Cov.: 33 AF XY: 0.401 AC XY: 29790 AN XY: 74370

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.412

Alfa AF: 0.477 Hom.: 23371

Bravo AF: 0.382

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.65

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: rs270413; hg19: chr6-7749643;