6-7819662-C-T

Variant names:

• chr6-7819662-C-T
• rs267806
• NM_001718.6:c.665-25478C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001718.6(BMP6):​c.665-25478C>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 151,934 control chromosomes in the GnomAD database, including 12,257 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 (12257 hom., cov: 32)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 6 publications found

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]

BMP6 Gene-Disease associations (from GenCC):

• hemochromatosis type 5

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001718.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	NM_001718.6	MANE Select	c.665-25478C>T		intron	N/A	NP_001709.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	ENST00000283147.7	TSL:1 MANE Select	c.665-25478C>T		intron	N/A	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57775 AN: 151818 Hom.: 12227 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.381 AC: 57864 AN: 151934 Hom.: 12257 Cov.: 32 AF XY: 0.390 AC XY: 28951 AN XY: 74246

African (AFR) AF: 0.503 AC: 20842 AN: 41402

American (AMR) AF: 0.467 AC: 7124 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3468

East Asian (EAS) AF: 0.729 AC: 3759 AN: 5158

South Asian (SAS) AF: 0.365 AC: 1756 AN: 4814

European-Finnish (FIN) AF: 0.359 AC: 3793 AN: 10554

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18901 AN: 67956

Other (OTH) AF: 0.372 AC: 786 AN: 2114

Alfa AF: 0.345 Hom.: 1902

Bravo AF: 0.396

Asia WGS AF: 0.564 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.91
DANN	Benign	0.66
PhyloP100		0.14
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: rs267806; hg19: chr6-7819895;