chr6-7841888-G-T

Variant names:

• chr6-7841888-G-T
• rs267190
• NM_001718.6:c.665-3252G>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.665-3252G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,110 control chromosomes in the GnomAD database, including 17,633 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 0.47 (17633 hom., cov: 32)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	NM_001718.6	MANE Select	c.665-3252G>T		intron	N/A	NP_001709.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	ENST00000283147.7	TSL:1 MANE Select	c.665-3252G>T		intron	N/A	ENSP00000283147.6
	BMP6	ENST00000946083.1		c.665-3252G>T		intron	N/A	ENSP00000616142.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71719 AN: 151990 Hom.: 17596 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.472 AC: 71815 AN: 152110 Hom.: 17633 Cov.: 32 AF XY: 0.475 AC XY: 35338 AN XY: 74344

African (AFR) AF: 0.540 AC: 22414 AN: 41504

American (AMR) AF: 0.542 AC: 8293 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 969 AN: 3462

East Asian (EAS) AF: 0.768 AC: 3979 AN: 5178

South Asian (SAS) AF: 0.407 AC: 1957 AN: 4814

European-Finnish (FIN) AF: 0.433 AC: 4578 AN: 10570

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.412 AC: 27985 AN: 67982

Other (OTH) AF: 0.465 AC: 982 AN: 2110

Alfa AF: 0.460 Hom.: 2740

Bravo AF: 0.489

Asia WGS AF: 0.602 AC: 2092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.82
PhyloP100		-1.2
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: rs267190; hg19: chr6-7842121;