6-7768619-G-C

Variant names:

• chr6-7768619-G-C
• rs270393
• NM_001718.6:c.664+41000G>C

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+41000G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 151,890 control chromosomes in the GnomAD database, including 39,497 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 0.71 (39497 hom., cov: 31)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 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+41000G>C		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+41000G>C		intron	N/A	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107878 AN: 151772 Hom.: 39491 Cov.: 31

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.711 AC: 107922 AN: 151890 Hom.: 39497 Cov.: 31 AF XY: 0.709 AC XY: 52624 AN XY: 74226

African (AFR) AF: 0.525 AC: 21701 AN: 41350

American (AMR) AF: 0.784 AC: 11972 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2741 AN: 3472

East Asian (EAS) AF: 0.536 AC: 2760 AN: 5148

South Asian (SAS) AF: 0.664 AC: 3195 AN: 4814

European-Finnish (FIN) AF: 0.737 AC: 7791 AN: 10566

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55307 AN: 67960

Other (OTH) AF: 0.713 AC: 1505 AN: 2110

Alfa AF: 0.754 Hom.: 5183

Bravo AF: 0.707

Asia WGS AF: 0.615 AC: 2139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.40
PhyloP100		-1.9
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: rs270393; hg19: chr6-7768852;