rs4135221

Positions:

• chr9-110244957-G-A

Variant summary

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

The NM_003329.4(TXN):​c.190-114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 687,600 control chromosomes in the GnomAD database, including 4,496 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 0.12 (1135 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3361 hom.)
• Consequence: TXN NM_003329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.838

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXN	NM_003329.4	c.190-114C>T		intron_variant		ENST00000374517.6
TXN	NM_001244938.2	c.130-114C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXN	ENST00000374517.6	c.190-114C>T		intron_variant		1	NM_003329.4	P1
TXN	ENST00000374515.9	c.130-114C>T		intron_variant		1
TXN	ENST00000487892.1	n.160C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17690 AN: 151984 Hom.: 1135 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0763

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0501

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.108 AC: 57769 AN: 535498 Hom.: 3361 Cov.: 7 AF XY: 0.108 AC XY: 30743 AN XY: 285748

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.0610

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.0455

Gnomad4 SAS exome AF: 0.0894

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.116 AC: 17698 AN: 152102 Hom.: 1135 Cov.: 32 AF XY: 0.115 AC XY: 8514 AN XY: 74344

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0762

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0500

Gnomad4 SAS AF: 0.0851

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.102

Alfa AF: 0.113 Hom.: 466

Bravo AF: 0.115

Asia WGS AF: 0.0690 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.5
DANN	Benign	0.67

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: rs4135221; hg19: chr9-113007237;