rs267184

Variant names:

• chr6-7833196-G-A
• rs267184
• NM_001718.6:c.665-11944G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-7833196-G-A
• chr6-7833196-G-C

Variant summary

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

The NM_001718.6(BMP6):​c.665-11944G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,944 control chromosomes in the GnomAD database, including 22,986 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 0.54 (22986 hom., cov: 31)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.665-11944G>A		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.665-11944G>A		intron_variant	Intron 1 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81337 AN: 151826 Hom.: 22940 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.536 AC: 81447 AN: 151944 Hom.: 22986 Cov.: 31 AF XY: 0.537 AC XY: 39888 AN XY: 74266

African (AFR) AF: 0.695 AC: 28787 AN: 41414

American (AMR) AF: 0.579 AC: 8844 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1211 AN: 3462

East Asian (EAS) AF: 0.725 AC: 3725 AN: 5138

South Asian (SAS) AF: 0.425 AC: 2049 AN: 4822

European-Finnish (FIN) AF: 0.483 AC: 5108 AN: 10574

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29960 AN: 67942

Other (OTH) AF: 0.521 AC: 1099 AN: 2108

Alfa AF: 0.473 Hom.: 11700

Bravo AF: 0.558

Asia WGS AF: 0.612 AC: 2129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.36
PhyloP100		0.32
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: rs267184; hg19: chr6-7833429;