NM_001718.6:c.664+8891C>T

Variant names:

• chr6-7736510-C-T
• rs2068361
• NM_001718.6:c.664+8891C>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.664+8891C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,108 control chromosomes in the GnomAD database, including 4,825 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 0.25 (4825 hom., cov: 33)
• Consequence: BMP6 NM_001718.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP6	NM_001718.6	c.664+8891C>T		intron_variant	Intron 1 of 6	ENST00000283147.7	NP_001709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7	c.664+8891C>T		intron_variant	Intron 1 of 6	1	NM_001718.6	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38025 AN: 151990 Hom.: 4817 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.250 AC: 38056 AN: 152108 Hom.: 4825 Cov.: 33 AF XY: 0.251 AC XY: 18667 AN XY: 74364

African (AFR) AF: 0.239 AC: 9903 AN: 41500

American (AMR) AF: 0.293 AC: 4476 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3470

East Asian (EAS) AF: 0.259 AC: 1339 AN: 5172

South Asian (SAS) AF: 0.155 AC: 748 AN: 4828

European-Finnish (FIN) AF: 0.224 AC: 2371 AN: 10570

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.252 AC: 17159 AN: 67974

Other (OTH) AF: 0.267 AC: 565 AN: 2114

Alfa AF: 0.259 Hom.: 23010

Bravo AF: 0.260

Asia WGS AF: 0.212 AC: 737 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.0
DANN	Benign	0.76
PhyloP100		-0.47
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: rs2068361; hg19: chr6-7736743;