rs2017869

Variant names:

• chr22-24601342-G-C
• rs2017869
• ENST00000652248.1:n.*168-6612G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-24601342-G-C
• chr22-24601342-G-T

Variant summary

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

The ENST00000652248.1(ENSG00000286070):​n.*168-6612G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 145,394 control chromosomes in the GnomAD database, including 21,863 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 0.52 (21863 hom., cov: 33)
• Consequence: ENSG00000286070 ENST00000652248.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 17 publications found

Genes affected

ENSG00000286070 (HGNC:):

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]

GGT1 Gene-Disease associations (from GenCC):

• gamma-glutamyl transpeptidase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGT1	NM_013430.3	c.-428-6612G>C		intron_variant	Intron 1 of 15		NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286070	ENST00000652248.1	n.*168-6612G>C		intron_variant	Intron 5 of 19			ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 75957 AN: 145278 Hom.: 21826 Cov.: 33

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.523 AC: 76050 AN: 145394 Hom.: 21863 Cov.: 33 AF XY: 0.516 AC XY: 36569 AN XY: 70830

African (AFR) AF: 0.804 AC: 33140 AN: 41232

American (AMR) AF: 0.526 AC: 7651 AN: 14554

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1587 AN: 3294

East Asian (EAS) AF: 0.402 AC: 1917 AN: 4764

South Asian (SAS) AF: 0.327 AC: 1427 AN: 4364

European-Finnish (FIN) AF: 0.360 AC: 3518 AN: 9774

Middle Eastern (MID) AF: 0.573 AC: 164 AN: 286

European-Non Finnish (NFE) AF: 0.395 AC: 25375 AN: 64264

Other (OTH) AF: 0.506 AC: 1026 AN: 2028

Alfa AF: 0.442 Hom.: 1974

Bravo AF: 0.529

Asia WGS AF: 0.400 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		-0.21
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2017869; hg19: chr22-24997309;