rs4820599

Variant names:

• chr22-24594246-A-G
• rs4820599
• ENST00000652248.1:n.*167+10438A>G

Variant summary

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

The NM_013430.3(GGT1):​c.-429+10438A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,928 control chromosomes in the GnomAD database, including 17,008 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 0.42 (17008 hom., cov: 31)
• Consequence: GGT1 NM_013430.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 51 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013430.3. 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_013430.3		c.-429+10438A>G		intron	N/A	NP_038347.2	P19440-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286070	ENST00000652248.1		n.*167+10438A>G		intron	N/A	ENSP00000499210.1
	ENSG00000286070	ENST00000404603.5	TSL:5	n.*167+10438A>G		intron	N/A	ENSP00000456090.1
	ENSG00000286070	ENST00000439775.1	TSL:3	n.*162+10438A>G		intron	N/A	ENSP00000456969.1	H3BT13

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64440 AN: 151810 Hom.: 16977 Cov.: 31

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.425 AC: 64527 AN: 151928 Hom.: 17008 Cov.: 31 AF XY: 0.417 AC XY: 30921 AN XY: 74232

African (AFR) AF: 0.749 AC: 31017 AN: 41428

American (AMR) AF: 0.437 AC: 6679 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3468

East Asian (EAS) AF: 0.233 AC: 1202 AN: 5152

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4812

European-Finnish (FIN) AF: 0.233 AC: 2456 AN: 10558

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19678 AN: 67918

Other (OTH) AF: 0.407 AC: 859 AN: 2108

Alfa AF: 0.332 Hom.: 33810

Bravo AF: 0.458

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.70
PhyloP100		0.12
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: rs4820599; hg19: chr22-24990213;