rs2001180

Positions:

• chr22-24608239-T-G

Variant summary

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

The NM_001288833.2(GGT1):​c.-359+216T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,024 control chromosomes in the GnomAD database, including 16,146 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 0.44 (16146 hom., cov: 32)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

Genes affected

GGT1 (HGNC:4250): (gamma-glutamyltransferase 1) The enzyme encoded by this gene is a type I gamma-glutamyltransferase that catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors. The enzyme is composed of a heavy chain and a light chain, which are derived from a single precursor protein. It is expressed in tissues involved in absorption and secretion and may contribute to the etiology of diabetes and other metabolic disorders. Multiple alternatively spliced variants have been identified. There are a number of related genes present on chromosomes 20 and 22, and putative pseudogenes for this gene on chromosomes 2, 13, and 22. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGT1	NM_001288833.2	c.-359+216T>G		intron_variant		ENST00000400382.6	NP_001275762.1
GGT1	NM_013421.3	c.-493+216T>G		intron_variant			NP_038265.2
GGT1	NM_013430.3	c.-359+216T>G		intron_variant			NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6	c.-359+216T>G		intron_variant		2	NM_001288833.2	ENSP00000383232	P1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67274 AN: 151906 Hom.: 16123 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.443 AC: 67342 AN: 152024 Hom.: 16146 Cov.: 32 AF XY: 0.437 AC XY: 32469 AN XY: 74308

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.441

Alfa AF: 0.414 Hom.: 1684

Bravo AF: 0.466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.86

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: rs2001180; hg19: chr22-25004206; COSMIC: COSV50640965; COSMIC: COSV50640965;