rs7211

Positions:

• chr1-145993449-G-A
• chr1-145993449-G-C
• chr1-145993449-G-T

Variant summary

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

The NM_006472.6(TXNIP):​c.*402C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 164,592 control chromosomes in the GnomAD database, including 6,451 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 0.20 (6315 hom., cov: 32)
  • Exomes 𝑓: 0.11 (136 hom.)
• Consequence: TXNIP NM_006472.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

Genes affected

TXNIP (HGNC:16952): (thioredoxin interacting protein) This gene encodes a thioredoxin-binding protein that is a member of the alpha arrestin protein family. Thioredoxin is a thiol-oxidoreductase that is a major regulator of cellular redox signaling which protects cells from oxidative stress. This protein inhibits the antioxidative function of thioredoxin resulting in the accumulation of reactive oxygen species and cellular stress. This protein also functions as a regulator of cellular metabolism and of endoplasmic reticulum (ER) stress. This protein may also function as a tumor suppressor. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNIP	NM_006472.6	c.*402C>T		3_prime_UTR_variant	8/8	ENST00000582401.6	NP_006463.3
TXNIP	NM_001313972.2	c.*402C>T		3_prime_UTR_variant	7/7		NP_001300901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNIP	ENST00000582401	c.*402C>T		3_prime_UTR_variant	8/8	1	NM_006472.6	ENSP00000462521.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30277 AN: 151790 Hom.: 6281 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.106 AC: 1339 AN: 12684 Hom.: 136 Cov.: 0 AF XY: 0.108 AC XY: 736 AN XY: 6794

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.0772

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0857

Gnomad4 NFE exome AF: 0.0445

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.200 AC: 30372 AN: 151908 Hom.: 6315 Cov.: 32 AF XY: 0.200 AC XY: 14845 AN XY: 74254

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.0435

Gnomad4 OTH AF: 0.161

Alfa AF: 0.0646 Hom.: 813

Bravo AF: 0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7211; hg19: chr1-145441620;