chr12-4315956-G-A

Position:

• chr12-4315956-G-A

Variant summary

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

The ENST00000635110.1(TIGAR):​c.-146+7200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,228 control chromosomes in the GnomAD database, including 55,595 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 0.83 (55595 hom., cov: 34)
• Consequence: TIGAR ENST00000635110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TIGAR	ENST00000635110.1	c.-146+7200G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126960 AN: 152110 Hom.: 55605 Cov.: 34

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.983

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.834 AC: 126981 AN: 152228 Hom.: 55595 Cov.: 34 AF XY: 0.831 AC XY: 61870 AN XY: 74420

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.957

Gnomad4 NFE AF: 0.983

Gnomad4 OTH AF: 0.853

Alfa AF: 0.941 Hom.: 96056

Bravo AF: 0.810

Asia WGS AF: 0.677 AC: 2357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10849033; hg19: chr12-4425122;