rs270417

Variant names:

• chr6-7729381-C-T
• rs270417
• NM_001718.6:c.664+1762C>T

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+1762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 149,220 control chromosomes in the GnomAD database, including 46,642 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 0.79 (46642 hom., cov: 22)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.664+1762C>T		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+1762C>T		intron_variant	Intron 1 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.786 AC: 117212 AN: 149102 Hom.: 46580 Cov.: 22

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.577

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.786 AC: 117338 AN: 149220 Hom.: 46642 Cov.: 22 AF XY: 0.790 AC XY: 57381 AN XY: 72634

African (AFR) AF: 0.895 AC: 36147 AN: 40374

American (AMR) AF: 0.777 AC: 11608 AN: 14934

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2195 AN: 3452

East Asian (EAS) AF: 0.963 AC: 4818 AN: 5004

South Asian (SAS) AF: 0.857 AC: 3981 AN: 4644

European-Finnish (FIN) AF: 0.768 AC: 7792 AN: 10140

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.719 AC: 48459 AN: 67428

Other (OTH) AF: 0.738 AC: 1516 AN: 2054

Alfa AF: 0.736 Hom.: 89915

Bravo AF: 0.786

Asia WGS AF: 0.923 AC: 3211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.6
DANN	Benign	0.89
PhyloP100		0.079
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: rs270417; hg19: chr6-7729614;