rs41302895

Positions:

• chr6-7881521-A-T

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP6	NM_001718.6	c.*1178A>T		3_prime_UTR_variant	7/7	ENST00000283147.7	NP_001709.1
TXNDC5	NM_030810.5	c.*1623T>A		3_prime_UTR_variant	10/10	ENST00000379757.9	NP_110437.2
BLOC1S5-TXNDC5	NR_037616.1	n.3081T>A		non_coding_transcript_exon_variant	13/13
TXNDC5	NM_001145549.4	c.*1623T>A		3_prime_UTR_variant	10/10		NP_001139021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP6	ENST00000283147.7	c.*1178A>T		3_prime_UTR_variant	7/7	1	NM_001718.6	ENSP00000283147	P1
TXNDC5	ENST00000379757.9	c.*1623T>A		3_prime_UTR_variant	10/10	1	NM_030810.5	ENSP00000369081	P1
TXNDC5	ENST00000460138.5	n.2700T>A		non_coding_transcript_exon_variant	4/4	2

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

Gnomad4 FIN exome AF: 0.148

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0486

Gnomad4 EAS AF: 0.000839

Gnomad4 SAS AF: 0.0654

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0739

Gnomad4 OTH AF: 0.0361

Alfa AF: 0.0635 Hom.: 41

Bravo AF: 0.0445

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.087
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs41302895; hg19: chr6-7881754; COSMIC: COSV51663475; COSMIC: COSV51663475;