chr6-7853358-A-G

Variant names:

• chr6-7853358-A-G
• rs267201
• NM_001718.6:c.857+8026A>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.857+8026A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,992 control chromosomes in the GnomAD database, including 12,533 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 0.39 (12533 hom., cov: 32)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 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.857+8026A>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.857+8026A>G		intron	N/A	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59711 AN: 151872 Hom.: 12519 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.393 AC: 59764 AN: 151992 Hom.: 12533 Cov.: 32 AF XY: 0.399 AC XY: 29622 AN XY: 74300

African (AFR) AF: 0.353 AC: 14640 AN: 41424

American (AMR) AF: 0.491 AC: 7503 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3468

East Asian (EAS) AF: 0.775 AC: 4003 AN: 5166

South Asian (SAS) AF: 0.401 AC: 1936 AN: 4822

European-Finnish (FIN) AF: 0.385 AC: 4062 AN: 10552

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.372 AC: 25290 AN: 67984

Other (OTH) AF: 0.396 AC: 835 AN: 2106

Alfa AF: 0.375 Hom.: 5696

Bravo AF: 0.405

Asia WGS AF: 0.588 AC: 2044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.52
PhyloP100		0.45
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: rs267201; hg19: chr6-7853591;