rs4755

Variant names:

• chr1-145992806-T-A
• rs4755
• NM_006472.6:c.*1045A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-145992806-T-A
• chr1-145992806-T-C
• chr1-145992806-T-G

Variant summary

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

The NM_006472.6(TXNIP):​c.*1045A>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 0.153 in 152,516 control chromosomes in the GnomAD database, including 3,264 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 0.15 (3262 hom., cov: 32)
  • Exomes 𝑓: 0.064 (2 hom.)
• Consequence: TXNIP NM_006472.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 11 publications found

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

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

• BP4: Computational evidence support a benign effect (Cadd=10.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006472.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNIP	NM_006472.6	MANE Select	c.*1045A>T		3_prime_UTR	Exon 8 of 8	NP_006463.3
	TXNIP	NM_001313972.2		c.*1045A>T		3_prime_UTR	Exon 7 of 7	NP_001300901.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNIP	ENST00000582401.6	TSL:1 MANE Select	c.*1045A>T		3_prime_UTR	Exon 8 of 8	ENSP00000462521.1
	TXNIP	ENST00000883755.1		c.*1045A>T		3_prime_UTR	Exon 8 of 8	ENSP00000553814.1
	TXNIP	ENST00000883753.1		c.*1045A>T		3_prime_UTR	Exon 8 of 8	ENSP00000553812.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23202 AN: 151926 Hom.: 3245 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.0584

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0472

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.0636 AC: 30 AN: 472 Hom.: 2 Cov.: 0 AF XY: 0.0646 AC XY: 19 AN XY: 294

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.0535 AC: 23 AN: 430

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0714 AC: 2 AN: 28

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.153 AC: 23259 AN: 152044 Hom.: 3262 Cov.: 32 AF XY: 0.154 AC XY: 11484 AN XY: 74362

African (AFR) AF: 0.362 AC: 14990 AN: 41392

American (AMR) AF: 0.173 AC: 2642 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0472 AC: 164 AN: 3472

East Asian (EAS) AF: 0.176 AC: 913 AN: 5176

South Asian (SAS) AF: 0.132 AC: 636 AN: 4820

European-Finnish (FIN) AF: 0.0644 AC: 682 AN: 10598

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0423 AC: 2875 AN: 68004

Other (OTH) AF: 0.132 AC: 278 AN: 2112

Alfa AF: 0.0344 Hom.: 52

Bravo AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	10
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4755;