rs4135225

Positions:

• chr9-110244411-G-A
• chr9-110244411-G-C
• chr9-110244411-G-T

Variant summary

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

The NM_003329.4(TXN):​c.256-192C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 150,900 control chromosomes in the GnomAD database, including 39,054 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 0.71 (39054 hom., cov: 29)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXN	NM_003329.4	c.256-192C>T		intron_variant		ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.196-192C>T		intron_variant			NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.256-192C>T		intron_variant		1	NM_003329.4	ENSP00000363641	P1
TXN	ENST00000374515.9	c.196-192C>T		intron_variant		1		ENSP00000363639
TXN	ENST00000487892.1	n.340-192C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.714 AC: 107676 AN: 150794 Hom.: 39001 Cov.: 29

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.667

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.714 AC: 107780 AN: 150900 Hom.: 39054 Cov.: 29 AF XY: 0.715 AC XY: 52724 AN XY: 73718

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.716

Alfa AF: 0.692 Hom.: 4549

Bravo AF: 0.730

Asia WGS AF: 0.886 AC: 3060 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.22

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: rs4135225; hg19: chr9-113006691;