chr6-7872119-C-T

Variant names:

• chr6-7872119-C-T
• rs449853
• NM_001718.6:c.1205-6955C>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.1205-6955C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,918 control chromosomes in the GnomAD database, including 13,657 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 0.41 (13657 hom., cov: 31)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• 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
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 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.1205-6955C>T		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.1205-6955C>T		intron	N/A	ENSP00000283147.6	P22004
	BMP6	ENST00000946083.1		c.1205-6955C>T		intron	N/A	ENSP00000616142.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62804 AN: 151802 Hom.: 13621 Cov.: 31

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.414 AC: 62892 AN: 151918 Hom.: 13657 Cov.: 31 AF XY: 0.421 AC XY: 31249 AN XY: 74268

African (AFR) AF: 0.416 AC: 17217 AN: 41418

American (AMR) AF: 0.522 AC: 7974 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 942 AN: 3464

East Asian (EAS) AF: 0.767 AC: 3960 AN: 5164

South Asian (SAS) AF: 0.389 AC: 1871 AN: 4806

European-Finnish (FIN) AF: 0.435 AC: 4577 AN: 10532

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.366 AC: 24882 AN: 67944

Other (OTH) AF: 0.418 AC: 884 AN: 2114

Alfa AF: 0.388 Hom.: 1454

Bravo AF: 0.427

Asia WGS AF: 0.588 AC: 2044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.54
PhyloP100		0.085
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: rs449853; hg19: chr6-7872352;