6-7860582-C-T

Variant names:

• chr6-7860582-C-T
• rs267206
• NM_001718.6:c.858-869C>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.858-869C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,088 control chromosomes in the GnomAD database, including 45,874 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 0.77 (45874 hom., cov: 31)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.858-869C>T		intron_variant	Intron 2 of 6	ENST00000283147.7	NP_001709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7	c.858-869C>T		intron_variant	Intron 2 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116958 AN: 151970 Hom.: 45851 Cov.: 31

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.769 AC: 117023 AN: 152088 Hom.: 45874 Cov.: 31 AF XY: 0.777 AC XY: 57777 AN XY: 74364

African (AFR) AF: 0.625 AC: 25881 AN: 41434

American (AMR) AF: 0.816 AC: 12473 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2636 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5167 AN: 5174

South Asian (SAS) AF: 0.948 AC: 4575 AN: 4824

European-Finnish (FIN) AF: 0.841 AC: 8909 AN: 10596

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54849 AN: 67978

Other (OTH) AF: 0.759 AC: 1603 AN: 2112

Alfa AF: 0.805 Hom.: 31370

Bravo AF: 0.761

Asia WGS AF: 0.945 AC: 3286 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	7.6
DANN	Benign	0.47
PhyloP100		0.71
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: rs267206; hg19: chr6-7860815;