rs7310505

Variant names:

• chr12-104260770-A-C
• rs7310505
• NM_001093771.3:c.304+2691A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-104260770-A-C
• chr12-104260770-A-G
• chr12-104260770-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001093771.3(TXNRD1):​c.304+2691A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,028 control chromosomes in the GnomAD database, including 41,330 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 0.74 (41330 hom., cov: 32)
• Consequence: TXNRD1 NM_001093771.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 18 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD1	NM_001093771.3	c.304+2691A>C		intron_variant	Intron 3 of 16	ENST00000525566.6	NP_001087240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNRD1	ENST00000525566.6	c.304+2691A>C		intron_variant	Intron 3 of 16	1	NM_001093771.3	ENSP00000434516.1
TXNRD1	ENST00000526006.1	n.194+2691A>C		intron_variant	Intron 2 of 4	1

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111839 AN: 151910 Hom.: 41302 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.736 AC: 111918 AN: 152028 Hom.: 41330 Cov.: 32 AF XY: 0.731 AC XY: 54306 AN XY: 74296

African (AFR) AF: 0.723 AC: 29938 AN: 41424

American (AMR) AF: 0.709 AC: 10839 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2467 AN: 3468

East Asian (EAS) AF: 0.866 AC: 4481 AN: 5174

South Asian (SAS) AF: 0.685 AC: 3302 AN: 4818

European-Finnish (FIN) AF: 0.686 AC: 7243 AN: 10562

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51243 AN: 67988

Other (OTH) AF: 0.741 AC: 1564 AN: 2112

Alfa AF: 0.750 Hom.: 52587

Bravo AF: 0.742

Asia WGS AF: 0.743 AC: 2581 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.7
DANN	Benign	0.79
PhyloP100		-0.41
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: rs7310505; hg19: chr12-104654548;