6-7878333-C-T

Variant names:

• chr6-7878333-C-T
• rs267170
• NM_001718.6:c.1205-741C>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.1205-741C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,060 control chromosomes in the GnomAD database, including 10,768 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 0.36 (10768 hom., cov: 33)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.1205-741C>T		intron_variant	Intron 4 of 6	ENST00000283147.7	NP_001709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7	c.1205-741C>T		intron_variant	Intron 4 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55075 AN: 151942 Hom.: 10752 Cov.: 33

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.363 AC: 55132 AN: 152060 Hom.: 10768 Cov.: 33 AF XY: 0.365 AC XY: 27101 AN XY: 74328

African (AFR) AF: 0.451 AC: 18724 AN: 41480

American (AMR) AF: 0.478 AC: 7312 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 817 AN: 3470

East Asian (EAS) AF: 0.619 AC: 3171 AN: 5120

South Asian (SAS) AF: 0.293 AC: 1408 AN: 4812

European-Finnish (FIN) AF: 0.259 AC: 2736 AN: 10578

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19680 AN: 67978

Other (OTH) AF: 0.366 AC: 774 AN: 2114

Alfa AF: 0.239 Hom.: 799

Bravo AF: 0.387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.52
PhyloP100		-0.59
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: rs267170; hg19: chr6-7878566;