12-104347747-C-G

Variant names:

• chr12-104347747-C-G
• rs4246271
• NM_001093771.3:c.1882-606C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001093771.3. 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
	TXNRD1	NM_001093771.3	MANE Select	c.1882-606C>G		intron	N/A	NP_001087240.1
	TXNRD1	NM_003330.4		c.1588-606C>G		intron	N/A	NP_003321.3
	TXNRD1	NM_001261445.2		c.1582-606C>G		intron	N/A	NP_001248374.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNRD1	ENST00000525566.6	TSL:1 MANE Select	c.1882-606C>G		intron	N/A	ENSP00000434516.1
	TXNRD1	ENST00000526691.5	TSL:1	c.1588-606C>G		intron	N/A	ENSP00000435929.1
	TXNRD1	ENST00000503506.6	TSL:1	c.1432-606C>G		intron	N/A	ENSP00000421934.2

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

African (AFR) AF: 0.979 AC: 40693 AN: 41574

American (AMR) AF: 0.826 AC: 12636 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 3236 AN: 3472

East Asian (EAS) AF: 0.855 AC: 4435 AN: 5186

South Asian (SAS) AF: 0.915 AC: 4412 AN: 4822

European-Finnish (FIN) AF: 0.844 AC: 8946 AN: 10596

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.892 AC: 60654 AN: 68026

Other (OTH) AF: 0.912 AC: 1926 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.30
PhyloP100		-1.6
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: rs4246271; hg19: chr12-104741525;