rs4246271

Positions:

• chr12-104347747-C-G
• chr12-104347747-C-T

Variant summary

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

The NM_001093771.3(TXNRD1):​c.1882-606C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,286 control chromosomes in the GnomAD database, including 62,828 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 0.91 (62828 hom., cov: 32)
• Consequence: TXNRD1 NM_001093771.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNRD1	NM_001093771.3	c.1882-606C>G		intron_variant		ENST00000525566.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNRD1	ENST00000525566.6	c.1882-606C>G		intron_variant		1	NM_001093771.3	P1

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137941 AN: 152168 Hom.: 62780 Cov.: 32

Gnomad AFR AF: 0.979

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.906 AC: 138044 AN: 152286 Hom.: 62828 Cov.: 32 AF XY: 0.902 AC XY: 67176 AN XY: 74442

Gnomad4 AFR AF: 0.979

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.932

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.844

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.912

Alfa AF: 0.893 Hom.: 7068

Bravo AF: 0.907

Asia WGS AF: 0.877 AC: 3050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.30

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: rs4246271; hg19: chr12-104741525;