chr6-7743430-G-A

Variant names:

• chr6-7743430-G-A
• rs9505270
• NM_001718.6:c.664+15811G>A

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+15811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,096 control chromosomes in the GnomAD database, including 6,273 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 0.28 (6273 hom., cov: 32)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 11 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.664+15811G>A		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+15811G>A		intron_variant	Intron 1 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43234 AN: 151978 Hom.: 6250 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.285 AC: 43311 AN: 152096 Hom.: 6273 Cov.: 32 AF XY: 0.286 AC XY: 21238 AN XY: 74338

African (AFR) AF: 0.305 AC: 12642 AN: 41482

American (AMR) AF: 0.350 AC: 5347 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3468

East Asian (EAS) AF: 0.321 AC: 1659 AN: 5174

South Asian (SAS) AF: 0.163 AC: 787 AN: 4824

European-Finnish (FIN) AF: 0.251 AC: 2655 AN: 10562

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

European-Non Finnish (NFE) AF: 0.270 AC: 18330 AN: 67976

Other (OTH) AF: 0.273 AC: 577 AN: 2114

Alfa AF: 0.277 Hom.: 19159

Bravo AF: 0.299

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.78
DANN	Benign	0.82
PhyloP100		-0.18
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: rs9505270; hg19: chr6-7743663;