6-7869291-A-G

Variant names:

• chr6-7869291-A-G
• rs376308
• NM_001718.6:c.1204+6793A>G

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+6793A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,194 control chromosomes in the GnomAD database, including 8,656 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 0.33 (8656 hom., cov: 34)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.1204+6793A>G		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+6793A>G		intron_variant	Intron 4 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49506 AN: 152076 Hom.: 8637 Cov.: 34

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.326 AC: 49570 AN: 152194 Hom.: 8656 Cov.: 34 AF XY: 0.328 AC XY: 24375 AN XY: 74398

African (AFR) AF: 0.373 AC: 15491 AN: 41522

American (AMR) AF: 0.445 AC: 6805 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3468

East Asian (EAS) AF: 0.593 AC: 3061 AN: 5160

South Asian (SAS) AF: 0.288 AC: 1393 AN: 4830

European-Finnish (FIN) AF: 0.253 AC: 2684 AN: 10608

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18256 AN: 67990

Other (OTH) AF: 0.333 AC: 704 AN: 2114

Alfa AF: 0.263 Hom.: 3071

Bravo AF: 0.346

Asia WGS AF: 0.427 AC: 1483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.75
DANN	Benign	0.43
PhyloP100		-1.5
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: rs376308; hg19: chr6-7869524;