NM_001718.6:c.664+9956A>G

Variant names:

• chr6-7737575-A-G
• rs270406
• NM_001718.6:c.664+9956A>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.664+9956A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,864 control chromosomes in the GnomAD database, including 27,541 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 0.60 (27541 hom., cov: 31)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.664+9956A>G		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+9956A>G		intron_variant	Intron 1 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91105 AN: 151758 Hom.: 27510 Cov.: 31

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.600 AC: 91189 AN: 151864 Hom.: 27541 Cov.: 31 AF XY: 0.603 AC XY: 44760 AN XY: 74208

African (AFR) AF: 0.640 AC: 26486 AN: 41412

American (AMR) AF: 0.592 AC: 9035 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1722 AN: 3468

East Asian (EAS) AF: 0.578 AC: 2981 AN: 5160

South Asian (SAS) AF: 0.705 AC: 3389 AN: 4810

European-Finnish (FIN) AF: 0.636 AC: 6691 AN: 10524

Middle Eastern (MID) AF: 0.490 AC: 141 AN: 288

European-Non Finnish (NFE) AF: 0.573 AC: 38880 AN: 67912

Other (OTH) AF: 0.582 AC: 1225 AN: 2106

Alfa AF: 0.568 Hom.: 52022

Bravo AF: 0.593

Asia WGS AF: 0.659 AC: 2291 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.44
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: rs270406; hg19: chr6-7737808;