6-7738159-T-C

Variant names:

• chr6-7738159-T-C
• rs270407
• NM_001718.6:c.664+10540T>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.664+10540T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,112 control chromosomes in the GnomAD database, including 4,507 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 0.23 (4507 hom., cov: 32)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.664+10540T>C		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.664+10540T>C		intron_variant	Intron 1 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35603 AN: 151996 Hom.: 4508 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.234 AC: 35601 AN: 152112 Hom.: 4507 Cov.: 32 AF XY: 0.239 AC XY: 17737 AN XY: 74334

African (AFR) AF: 0.173 AC: 7200 AN: 41510

American (AMR) AF: 0.260 AC: 3979 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3468

East Asian (EAS) AF: 0.510 AC: 2629 AN: 5158

South Asian (SAS) AF: 0.350 AC: 1685 AN: 4818

European-Finnish (FIN) AF: 0.274 AC: 2898 AN: 10572

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15549 AN: 67974

Other (OTH) AF: 0.252 AC: 531 AN: 2110

Alfa AF: 0.232 Hom.: 6182

Bravo AF: 0.230

Asia WGS AF: 0.378 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.43
PhyloP100		0.56
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: rs270407; hg19: chr6-7738392;