rs4135218

Variant names:

• chr9-110245081-T-C
• rs4135218
• NM_003329.4:c.190-238A>G

Variant summary

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

The NM_003329.4(TXN):​c.190-238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 331,572 control chromosomes in the GnomAD database, including 37,642 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 (19458 hom., cov: 31)
  • Exomes 𝑓: 0.44 (18184 hom.)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 9 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.190-238A>G		intron_variant	Intron 3 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.130-238A>G		intron_variant	Intron 2 of 3		NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.190-238A>G		intron_variant	Intron 3 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.130-238A>G		intron_variant	Intron 2 of 3	1		ENSP00000363639.5
TXN	ENST00000487892.1	n.36A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74665 AN: 151880 Hom.: 19437 Cov.: 31

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.442 AC: 79372 AN: 179574 Hom.: 18184 Cov.: 0 AF XY: 0.442 AC XY: 42116 AN XY: 95300

African (AFR) AF: 0.679 AC: 4501 AN: 6632

American (AMR) AF: 0.399 AC: 3825 AN: 9596

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 2597 AN: 5396

East Asian (EAS) AF: 0.337 AC: 4485 AN: 13290

South Asian (SAS) AF: 0.438 AC: 9292 AN: 21218

European-Finnish (FIN) AF: 0.360 AC: 3159 AN: 8782

Middle Eastern (MID) AF: 0.539 AC: 921 AN: 1708

European-Non Finnish (NFE) AF: 0.446 AC: 45831 AN: 102708

Other (OTH) AF: 0.465 AC: 4761 AN: 10244

GnomAD4 genome AF: 0.492 AC: 74733 AN: 151998 Hom.: 19458 Cov.: 31 AF XY: 0.483 AC XY: 35919 AN XY: 74298

African (AFR) AF: 0.673 AC: 27882 AN: 41430

American (AMR) AF: 0.441 AC: 6734 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1622 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1818 AN: 5174

South Asian (SAS) AF: 0.426 AC: 2050 AN: 4812

European-Finnish (FIN) AF: 0.322 AC: 3399 AN: 10554

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29648 AN: 67976

Other (OTH) AF: 0.509 AC: 1076 AN: 2114

Alfa AF: 0.459 Hom.: 10247

Bravo AF: 0.508

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4135218; hg19: chr9-113007361;