NM_001718.6:c.*735A>G

Variant names:

• chr6-7881078-A-G
• rs1044104
• NM_001718.6:c.*735A>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.*735A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,204 control chromosomes in the GnomAD database, including 9,915 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 0.35 (9910 hom., cov: 33)
  • Exomes 𝑓: 0.27 (5 hom.)
• Consequence: BMP6 NM_001718.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 13 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]

BLOC1S5-TXNDC5 (HGNC:42001): (BLOC1S5-TXNDC5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MUTED (muted homolog) and TXNDC5 (thioredoxin domain containing 5) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 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.*735A>G		3_prime_UTR	Exon 7 of 7	NP_001709.1
	BLOC1S5-TXNDC5	NR_037616.1		n.*172T>C		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	ENST00000283147.7	TSL:1 MANE Select	c.*735A>G		3_prime_UTR	Exon 7 of 7	ENSP00000283147.6

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52619 AN: 151998 Hom.: 9886 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.273 AC: 24 AN: 88 Hom.: 5 Cov.: 0 AF XY: 0.300 AC XY: 15 AN XY: 50

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.237 AC: 18 AN: 76

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.346 AC: 52691 AN: 152116 Hom.: 9910 Cov.: 33 AF XY: 0.349 AC XY: 25975 AN XY: 74372

African (AFR) AF: 0.424 AC: 17566 AN: 41470

American (AMR) AF: 0.455 AC: 6947 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 832 AN: 3468

East Asian (EAS) AF: 0.657 AC: 3402 AN: 5180

South Asian (SAS) AF: 0.301 AC: 1455 AN: 4826

European-Finnish (FIN) AF: 0.263 AC: 2786 AN: 10576

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18469 AN: 67998

Other (OTH) AF: 0.345 AC: 729 AN: 2112

Alfa AF: 0.309 Hom.: 12260

Bravo AF: 0.368

Asia WGS AF: 0.469 AC: 1631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.14
DANN	Benign	0.33
PhyloP100		-1.1
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: rs1044104; hg19: chr6-7881311;