rs267196

Variant names:

• chr6-7849102-T-A
• rs267196
• NM_001718.6:c.857+3770T>A

Variant summary

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

The NM_001718.6(BMP6):​c.857+3770T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,996 control chromosomes in the GnomAD database, including 11,569 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 (11569 hom., cov: 32)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 7 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
• iron overload, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	NM_001718.6	MANE Select	c.857+3770T>A		intron	N/A	NP_001709.1	P22004

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	ENST00000283147.7	TSL:1 MANE Select	c.857+3770T>A		intron	N/A	ENSP00000283147.6	P22004
	BMP6	ENST00000946083.1		c.857+3770T>A		intron	N/A	ENSP00000616142.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57276 AN: 151878 Hom.: 11562 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.377 AC: 57315 AN: 151996 Hom.: 11569 Cov.: 32 AF XY: 0.384 AC XY: 28548 AN XY: 74280

African (AFR) AF: 0.296 AC: 12271 AN: 41468

American (AMR) AF: 0.483 AC: 7375 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3694 AN: 5154

South Asian (SAS) AF: 0.390 AC: 1878 AN: 4814

European-Finnish (FIN) AF: 0.422 AC: 4456 AN: 10558

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.373 AC: 25341 AN: 67954

Other (OTH) AF: 0.381 AC: 805 AN: 2114

Alfa AF: 0.363 Hom.: 1284

Bravo AF: 0.384

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.58
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs267196; hg19: chr6-7849335;