chr6-7845011-C-T

Variant names:

• chr6-7845011-C-T
• rs267192
• NM_001718.6:c.665-129C>T

Variant summary

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

The NM_001718.6(BMP6):​c.665-129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 801,822 control chromosomes in the GnomAD database, including 68,673 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 (11896 hom., cov: 32)
  • Exomes 𝑓: 0.41 (56777 hom.)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.665-129C>T		intron_variant	Intron 1 of 6	ENST00000283147.7	NP_001709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7	c.665-129C>T		intron_variant	Intron 1 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58354 AN: 151882 Hom.: 11888 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.405 AC: 263227 AN: 649822 Hom.: 56777 AF XY: 0.402 AC XY: 135629 AN XY: 337410

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.747

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.384 AC: 58399 AN: 152000 Hom.: 11896 Cov.: 32 AF XY: 0.391 AC XY: 29077 AN XY: 74292

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.388

Alfa AF: 0.237 Hom.: 539

Bravo AF: 0.392

Asia WGS AF: 0.564 AC: 1961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.86
DANN	Benign	0.78

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: rs267192; hg19: chr6-7845244; COSMIC: COSV51661704;