6-7874000-T-G

Variant names:

• chr6-7874000-T-G
• rs1225929
• NM_001718.6:c.1205-5074T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001718.6(BMP6):​c.1205-5074T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• Publications: 3 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
• iron overload, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	NM_001718.6	MANE Select	c.1205-5074T>G		intron	N/A	NP_001709.1	P22004

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	ENST00000283147.7	TSL:1 MANE Select	c.1205-5074T>G		intron	N/A	ENSP00000283147.6	P22004
	BMP6	ENST00000946083.1		c.1205-5074T>G		intron	N/A	ENSP00000616142.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151674 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151674 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74024

African (AFR) AF: 0.00 AC: 0 AN: 41264

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.086
PhyloP100		-0.29

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: rs1225929; hg19: chr6-7874233;