rs41302895

Variant names:

• chr6-7881521-A-T
• rs41302895
• NM_001718.6:c.*1178A>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.*1178A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 151,032 control chromosomes in the GnomAD database, including 310 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 0.053 (307 hom., cov: 33)
  • Exomes 𝑓: 0.15 (3 hom.)
• Consequence: BMP6 NM_001718.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• 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]

TXNDC5 (HGNC:21073): (thioredoxin domain containing 5) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal endoplasmic reticulum (ER)-signal sequence, three catalytically active thioredoxin domains and a C-terminal ER-retention sequence. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S5 gene. [provided by RefSeq, Dec 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0722 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	NM_001718.6	MANE Select	c.*1178A>T		3_prime_UTR	Exon 7 of 7	NP_001709.1
	TXNDC5	NM_030810.5	MANE Select	c.*1623T>A		3_prime_UTR	Exon 10 of 10	NP_110437.2
	TXNDC5	NM_001145549.4		c.*1623T>A		3_prime_UTR	Exon 10 of 10	NP_001139021.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP6	ENST00000283147.7	TSL:1 MANE Select	c.*1178A>T		3_prime_UTR	Exon 7 of 7	ENSP00000283147.6
	TXNDC5	ENST00000379757.9	TSL:1 MANE Select	c.*1623T>A		3_prime_UTR	Exon 10 of 10	ENSP00000369081.4
	TXNDC5	ENST00000946227.1		c.*1623T>A		splice_region	Exon 9 of 9	ENSP00000616286.1

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 7997 AN: 150614 Hom.: 306 Cov.: 33

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0486

Gnomad EAS AF: 0.000836

Gnomad SAS AF: 0.0654

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.0364

GnomAD4 exome AF: 0.151 AC: 47 AN: 312 Hom.: 3 Cov.: 0 AF XY: 0.154 AC XY: 29 AN XY: 188

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

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: 0.148 AC: 46 AN: 310

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.0531 AC: 7999 AN: 150720 Hom.: 307 Cov.: 33 AF XY: 0.0538 AC XY: 3962 AN XY: 73636

African (AFR) AF: 0.0134 AC: 551 AN: 41122

American (AMR) AF: 0.0322 AC: 488 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.0486 AC: 168 AN: 3454

East Asian (EAS) AF: 0.000839 AC: 4 AN: 4770

South Asian (SAS) AF: 0.0654 AC: 311 AN: 4752

European-Finnish (FIN) AF: 0.113 AC: 1184 AN: 10468

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0739 AC: 5005 AN: 67724

Other (OTH) AF: 0.0361 AC: 75 AN: 2076

Alfa AF: 0.0635 Hom.: 41

Bravo AF: 0.0445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.087
DANN	Benign	0.52
PhyloP100		-1.3
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: rs41302895; hg19: chr6-7881754; COSMIC: COSV51663475; COSMIC: COSV51663475;