6-7874000-T-A

Variant names:

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

Variant summary

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

The NM_001718.6(BMP6):​c.1205-5074T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,702 control chromosomes in the GnomAD database, including 23,861 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 0.53 (23861 hom., cov: 30)
• 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

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 (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.1205-5074T>A		intron_variant	Intron 4 of 6	ENST00000283147.7	NP_001709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7	c.1205-5074T>A		intron_variant	Intron 4 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80508 AN: 151584 Hom.: 23802 Cov.: 30

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.532 AC: 80632 AN: 151702 Hom.: 23861 Cov.: 30 AF XY: 0.536 AC XY: 39690 AN XY: 74102

African (AFR) AF: 0.781 AC: 32289 AN: 41350

American (AMR) AF: 0.583 AC: 8896 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3466

East Asian (EAS) AF: 0.765 AC: 3919 AN: 5126

South Asian (SAS) AF: 0.398 AC: 1911 AN: 4798

European-Finnish (FIN) AF: 0.442 AC: 4635 AN: 10482

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26248 AN: 67908

Other (OTH) AF: 0.504 AC: 1062 AN: 2106

Alfa AF: 0.265 Hom.: 534

Bravo AF: 0.558

Asia WGS AF: 0.616 AC: 2140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.35
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;