NM_001718.6:c.665-24704G>A

Variant names:

• chr6-7820436-G-A
• rs11964227
• NM_001718.6:c.665-24704G>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.665-24704G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,106 control chromosomes in the GnomAD database, including 12,504 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 0.40 (12504 hom., cov: 32)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.771
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.437 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.665-24704G>A		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.665-24704G>A		intron	N/A	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60565 AN: 151988 Hom.: 12491 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.399 AC: 60618 AN: 152106 Hom.: 12504 Cov.: 32 AF XY: 0.394 AC XY: 29275 AN XY: 74354

African (AFR) AF: 0.348 AC: 14418 AN: 41474

American (AMR) AF: 0.356 AC: 5439 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1847 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1068 AN: 5170

South Asian (SAS) AF: 0.452 AC: 2183 AN: 4826

European-Finnish (FIN) AF: 0.419 AC: 4428 AN: 10570

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29873 AN: 67988

Other (OTH) AF: 0.389 AC: 823 AN: 2116

Alfa AF: 0.409 Hom.: 20047

Bravo AF: 0.393

Asia WGS AF: 0.318 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.78
PhyloP100		-0.77
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: rs11964227; hg19: chr6-7820669;