rs267202

Variant names:

• chr6-7854003-G-A
• rs267202
• NM_001718.6:c.858-7448G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-7854003-G-A
• chr6-7854003-G-C
• chr6-7854003-G-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.858-7448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,002 control chromosomes in the GnomAD database, including 12,709 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 (12709 hom., cov: 32)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.858-7448G>A		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.858-7448G>A		intron_variant	Intron 2 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60245 AN: 151884 Hom.: 12695 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.397 AC: 60297 AN: 152002 Hom.: 12709 Cov.: 32 AF XY: 0.402 AC XY: 29887 AN XY: 74286

African (AFR) AF: 0.364 AC: 15081 AN: 41454

American (AMR) AF: 0.494 AC: 7542 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3468

East Asian (EAS) AF: 0.774 AC: 4004 AN: 5170

South Asian (SAS) AF: 0.401 AC: 1936 AN: 4822

European-Finnish (FIN) AF: 0.386 AC: 4071 AN: 10538

Middle Eastern (MID) AF: 0.255 AC: 74 AN: 290

European-Non Finnish (NFE) AF: 0.372 AC: 25309 AN: 67966

Other (OTH) AF: 0.401 AC: 844 AN: 2106

Alfa AF: 0.402 Hom.: 5015

Bravo AF: 0.408

Asia WGS AF: 0.588 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.98
DANN	Benign	0.57
PhyloP100		0.065
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: rs267202; hg19: chr6-7854236;