chr12-4309618-T-C

Variant names:

• chr12-4309618-T-C
• rs12230555
• ENST00000674624.1:n.720+20628T>C

Variant summary

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

The ENST00000674624.1(ENSG00000285901):​n.720+20628T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 145,876 control chromosomes in the GnomAD database, including 18,393 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 0.47 (18393 hom., cov: 29)
• Consequence: ENSG00000285901 ENST00000674624.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 4 publications found

Genes affected

ENSG00000285901 (HGNC:):

TIGAR (HGNC:1185): (TP53 induced glycolysis regulatory phosphatase) This gene is regulated as part of the p53 tumor suppressor pathway and encodes a protein with sequence similarity to the bisphosphate domain of the glycolytic enzyme that degrades fructose-2,6-bisphosphate. The protein functions by blocking glycolysis and directing the pathway into the pentose phosphate shunt. Expression of this protein also protects cells from DNA damaging reactive oxygen species and provides some protection from DNA damage-induced apoptosis. The 12p13.32 region that includes this gene is paralogous to the 11q13.3 region. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285901	ENST00000674624.1	n.720+20628T>C		intron_variant	Intron 4 of 9			ENSP00000501898.1
TIGAR	ENST00000635110.1	c.-146+862T>C		intron_variant	Intron 1 of 5	5		ENSP00000488928.1
ENSG00000285901	ENST00000648100.1	n.720+20628T>C		intron_variant	Intron 4 of 11			ENSP00000497536.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 68238 AN: 145770 Hom.: 18376 Cov.: 29

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.468 AC: 68262 AN: 145876 Hom.: 18393 Cov.: 29 AF XY: 0.471 AC XY: 33570 AN XY: 71294

African (AFR) AF: 0.151 AC: 5675 AN: 37624

American (AMR) AF: 0.581 AC: 8739 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2328 AN: 3446

East Asian (EAS) AF: 0.516 AC: 2660 AN: 5158

South Asian (SAS) AF: 0.494 AC: 2328 AN: 4708

European-Finnish (FIN) AF: 0.560 AC: 5751 AN: 10274

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 38996 AN: 66370

Other (OTH) AF: 0.503 AC: 1028 AN: 2044

Alfa AF: 0.555 Hom.: 44268

Bravo AF: 0.452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.61
DANN	Benign	0.64
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs12230555; hg19: chr12-4418784;