rs911749

Variant names:

• chr6-7738726-G-A
• rs911749
• NM_001718.6:c.664+11107G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-7738726-G-A
• chr6-7738726-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000283147.7(BMP6):​c.664+11107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,138 control chromosomes in the GnomAD database, including 3,764 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 0.22 (3764 hom., cov: 33)
• Consequence: BMP6 ENST00000283147.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000283147.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	NM_001718.6	MANE Select	c.664+11107G>A		intron	N/A	NP_001709.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	ENST00000283147.7	TSL:1 MANE Select	c.664+11107G>A		intron	N/A	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33536 AN: 152020 Hom.: 3752 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.221 AC: 33576 AN: 152138 Hom.: 3764 Cov.: 33 AF XY: 0.223 AC XY: 16622 AN XY: 74390

African (AFR) AF: 0.189 AC: 7859 AN: 41484

American (AMR) AF: 0.276 AC: 4224 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3470

East Asian (EAS) AF: 0.321 AC: 1662 AN: 5174

South Asian (SAS) AF: 0.126 AC: 609 AN: 4828

European-Finnish (FIN) AF: 0.229 AC: 2419 AN: 10582

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15385 AN: 67992

Other (OTH) AF: 0.196 AC: 414 AN: 2108

Alfa AF: 0.219 Hom.: 7318

Bravo AF: 0.227

Asia WGS AF: 0.213 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.74
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: rs911749; hg19: chr6-7738959;