dbSNP rs5018287: TXNRD1:c.610+56A>G (chr12-104313373-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001093771.3(TXNRD1):c.610+56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,354,846 control chromosomes in the GnomAD database, including 196,151 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 0.49 ( 18544 hom., cov: 32)

Exomes 𝑓: 0.54 ( 177607 hom. )

Consequence

TXNRD1
NM_001093771.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.86

Publications

16 publications found

Variant links:

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]

TXNRD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNRD1	NM_001093771.3 link	c.610+56A>G		intron_variant	Intron 6 of 16	ENST00000525566.6	NP_001087240.1	Q16881-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNRD1	ENST00000525566.6 link	c.610+56A>G		intron_variant	Intron 6 of 16	1	NM_001093771.3	ENSP00000434516.1		Q16881-1

Frequencies

GnomAD3 genomes

AF:

0.488

AC:

74105

AN:

151932

Hom.:

18534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.520

GnomAD4 exome

AF:

0.542

AC:

651366

AN:

1202796

Hom.:

177607

AF XY:

0.541

AC XY:

323520

AN XY:

598552

show subpopulations

African (AFR)

AF:

0.372

AC:

9765

AN:

26270

American (AMR)

AF:

0.516

AC:

13315

AN:

25800

Ashkenazi Jewish (ASJ)

AF:

0.552

AC:

12219

AN:

22142

East Asian (EAS)

AF:

0.600

AC:

20398

AN:

34012

South Asian (SAS)

AF:

0.505

AC:

34083

AN:

67486

European-Finnish (FIN)

AF:

0.433

AC:

20807

AN:

48098

Middle Eastern (MID)

AF:

0.493

AC:

2543

AN:

5162

European-Non Finnish (NFE)

AF:

0.554

AC:

510995

AN:

922874

Other (OTH)

AF:

0.535

AC:

27241

AN:

50952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

14081

28162

42244

56325

70406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.488

AC:

74148

AN:

152050

Hom.:

18544

Cov.:

AF XY:

0.481

AC XY:

35781

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.381

AC:

15807

AN:

41468

American (AMR)

AF:

0.506

AC:

7723

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1815

AN:

3466

East Asian (EAS)

AF:

0.621

AC:

3217

AN:

5182

South Asian (SAS)

AF:

0.518

AC:

2498

AN:

4826

European-Finnish (FIN)

AF:

0.407

AC:

4293

AN:

10556

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.545

AC:

37066

AN:

67966

Other (OTH)

AF:

0.523

AC:

1102

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1935

3869

5804

7738

9673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.524

Hom.:

8887

Bravo

AF:

0.493

Asia WGS

AF:

0.542

AC:

1884

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.19

(source)

DANN

Benign

0.41

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs5018287

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over