chr22-24608239-T-G

Variant names:

• chr22-24608239-T-G
• rs2001180
• NM_001288833.2:c.-359+216T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

GGT1 Gene-Disease associations (from GenCC):

• gamma-glutamyl transpeptidase deficiency

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

ENSG00000286070 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288833.2. 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
	GGT1	NM_001288833.2	MANE Select	c.-359+216T>G		intron	N/A	NP_001275762.1	P19440-1
	GGT1	NM_013421.3		c.-493+216T>G		intron	N/A	NP_038265.2	A0A140VJJ9
	GGT1	NM_013430.3		c.-359+216T>G		intron	N/A	NP_038347.2	P19440-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGT1	ENST00000400382.6	TSL:2 MANE Select	c.-359+216T>G		intron	N/A	ENSP00000383232.1	P19440-1
	GGT1	ENST00000400380.5	TSL:1	c.-493+216T>G		intron	N/A	ENSP00000383231.1	P19440-1
	GGT1	ENST00000438643.6	TSL:1	c.-248+216T>G		intron	N/A	ENSP00000403826.2	C9JIY6

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

African (AFR) AF: 0.633 AC: 26244 AN: 41472

American (AMR) AF: 0.469 AC: 7174 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1546 AN: 3468

East Asian (EAS) AF: 0.382 AC: 1975 AN: 5172

South Asian (SAS) AF: 0.295 AC: 1420 AN: 4818

European-Finnish (FIN) AF: 0.317 AC: 3352 AN: 10570

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24312 AN: 67922

Other (OTH) AF: 0.441 AC: 930 AN: 2110

Alfa AF: 0.414 Hom.: 1684

Bravo AF: 0.466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.86
PhyloP100		0.037
Mutation Taster		=100/0	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: rs2001180; hg19: chr22-25004206; COSMIC: COSV50640965; COSMIC: COSV50640965;