rs270387

Variant names:

• chr6-7772759-A-G
• rs270387
• NM_001718.6:c.664+45140A>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+45140A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,056 control chromosomes in the GnomAD database, including 39,204 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 0.69 (39204 hom., cov: 31)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001718.6. 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+45140A>G		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+45140A>G		intron	N/A	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105632 AN: 151938 Hom.: 39196 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.695 AC: 105675 AN: 152056 Hom.: 39204 Cov.: 31 AF XY: 0.694 AC XY: 51543 AN XY: 74322

African (AFR) AF: 0.418 AC: 17327 AN: 41472

American (AMR) AF: 0.793 AC: 12118 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2876 AN: 3472

East Asian (EAS) AF: 0.537 AC: 2774 AN: 5164

South Asian (SAS) AF: 0.669 AC: 3221 AN: 4812

European-Finnish (FIN) AF: 0.760 AC: 8036 AN: 10574

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.836 AC: 56824 AN: 67968

Other (OTH) AF: 0.715 AC: 1511 AN: 2112

Alfa AF: 0.753 Hom.: 5578

Bravo AF: 0.687

Asia WGS AF: 0.616 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.61
PhyloP100		-0.99
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: rs270387; hg19: chr6-7772992;