rs408505

Variant names:

• chr6-7866194-T-C
• rs408505
• NM_001718.6:c.1204+3696T>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.1204+3696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,180 control chromosomes in the GnomAD database, including 20,255 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 0.50 (20255 hom., cov: 33)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.1204+3696T>C		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.1204+3696T>C		intron_variant	Intron 4 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75546 AN: 152062 Hom.: 20197 Cov.: 33

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.497 AC: 75664 AN: 152180 Hom.: 20255 Cov.: 33 AF XY: 0.500 AC XY: 37218 AN XY: 74402

African (AFR) AF: 0.671 AC: 27845 AN: 41496

American (AMR) AF: 0.570 AC: 8723 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1056 AN: 3470

East Asian (EAS) AF: 0.716 AC: 3707 AN: 5180

South Asian (SAS) AF: 0.400 AC: 1934 AN: 4830

European-Finnish (FIN) AF: 0.430 AC: 4557 AN: 10588

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26226 AN: 68002

Other (OTH) AF: 0.478 AC: 1010 AN: 2112

Alfa AF: 0.457 Hom.: 8670

Bravo AF: 0.519

Asia WGS AF: 0.589 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.40
DANN	Benign	0.49
PhyloP100		-1.4
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: rs408505; hg19: chr6-7866427;