rs4135179

Positions:

• chr9-110253720-T-C

Variant summary

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

The ENST00000374517.6(TXN):​c.25-2258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,252 control chromosomes in the GnomAD database, including 1,764 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 0.13 (1764 hom., cov: 32)
• Consequence: TXN ENST00000374517.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

Genes affected

TXN (HGNC:12435): (thioredoxin) The protein encoded by this gene acts as a homodimer and is involved in many redox reactions. The encoded protein is active in the reversible S-nitrosylation of cysteines in certain proteins, which is part of the response to intracellular nitric oxide. This protein is found in the cytoplasm. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXN	NM_003329.4	c.25-2258A>G		intron_variant		ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.25-2258A>G		intron_variant			NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.25-2258A>G		intron_variant		1	NM_003329.4	ENSP00000363641	P1
TXN	ENST00000374515.9	c.25-2258A>G		intron_variant		1		ENSP00000363639

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20104 AN: 152134 Hom.: 1764 Cov.: 32

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.132 AC: 20102 AN: 152252 Hom.: 1764 Cov.: 32 AF XY: 0.126 AC XY: 9404 AN XY: 74442

Gnomad4 AFR AF: 0.0356

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0606

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.108

Alfa AF: 0.182 Hom.: 2494

Bravo AF: 0.125

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.61

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: rs4135179; hg19: chr9-113016000; COSMIC: COSV65730978;