rs4135162

Variant names:

• chr9-110255625-C-G
• rs4135162
• NM_003329.4:c.24+787G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_003329.4(TXN):​c.24+787G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 152,332 control chromosomes in the GnomAD database, including 28 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 0.013 (28 hom., cov: 33)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0127 (1932/152332) while in subpopulation NFE AF = 0.0219 (1491/68030). AF 95% confidence interval is 0.021. There are 28 homozygotes in GnomAd4. There are 857 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXN	NM_003329.4	c.24+787G>C		intron_variant	Intron 1 of 4	ENST00000374517.6	NP_003320.2
TXN	NM_001244938.2	c.24+787G>C		intron_variant	Intron 1 of 3		NP_001231867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXN	ENST00000374517.6	c.24+787G>C		intron_variant	Intron 1 of 4	1	NM_003329.4	ENSP00000363641.5
TXN	ENST00000374515.9	c.24+787G>C		intron_variant	Intron 1 of 3	1		ENSP00000363639.5

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1932 AN: 152214 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.00362

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00687

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.00908

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

GnomAD4 genome AF: 0.0127 AC: 1932 AN: 152332 Hom.: 28 Cov.: 33 AF XY: 0.0115 AC XY: 857 AN XY: 74492

African (AFR) AF: 0.00361 AC: 150 AN: 41578

American (AMR) AF: 0.00379 AC: 58 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.00687 AC: 73 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1491 AN: 68030

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.0178 Hom.: 5

Bravo AF: 0.0122

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Benign	0.85
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=91/9	polymorphism

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: rs4135162; hg19: chr9-113017905;