rs11111979

Positions:

• chr12-104287004-C-G
• chr12-104287004-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000526691.5(TXNRD1):​c.-333C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,323,096 control chromosomes in the GnomAD database, including 184,757 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 0.47 (17428 hom., cov: 33)
  • Exomes 𝑓: 0.53 (167329 hom.)
• Consequence: TXNRD1 ENST00000526691.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88

Genes affected

TXNRD1 (HGNC:12437): (thioredoxin reductase 1) The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes an ubiquitously expressed, cytosolic form of TrxR, which functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternative splicing, primarily at the 5' end, results in transcript variants encoding same or different isoforms, including a glutaredoxin-containing isoform that is predominantly expressed in testis. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNRD1	NM_001093771.3	c.305-1927C>G		intron_variant		ENST00000525566.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNRD1	ENST00000525566.6	c.305-1927C>G		intron_variant		1	NM_001093771.3	P1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71180 AN: 151976 Hom.: 17426 Cov.: 33

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.532 AC: 622585 AN: 1171002 Hom.: 167329 Cov.: 59 AF XY: 0.530 AC XY: 298801 AN XY: 563252

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.533

Gnomad4 EAS exome AF: 0.610

Gnomad4 SAS exome AF: 0.487

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.541

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.468 AC: 71199 AN: 152094 Hom.: 17428 Cov.: 33 AF XY: 0.463 AC XY: 34412 AN XY: 74370

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.501

Alfa AF: 0.498 Hom.: 2413

Bravo AF: 0.470

Asia WGS AF: 0.543 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.71

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: rs11111979; hg19: chr12-104680782;