rs6519520

Variant names:

• chr22-24595928-A-G
• rs6519520
• ENST00000652248.1:n.*168-12026A>G

Variant summary

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

The ENST00000652248.1(ENSG00000286070):​n.*168-12026A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,174 control chromosomes in the GnomAD database, including 17,020 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 (17020 hom., cov: 33)
• Consequence: ENSG00000286070 ENST00000652248.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGT1	NM_013430.3	c.-428-12026A>G		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.*168-12026A>G		intron_variant	Intron 5 of 19			ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64501 AN: 152056 Hom.: 16989 Cov.: 33

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.232

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: 0.424 AC: 64588 AN: 152174 Hom.: 17020 Cov.: 33 AF XY: 0.416 AC XY: 30972 AN XY: 74408

African (AFR) AF: 0.748 AC: 31047 AN: 41490

American (AMR) AF: 0.437 AC: 6674 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1108 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1206 AN: 5188

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4826

European-Finnish (FIN) AF: 0.233 AC: 2469 AN: 10602

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

European-Non Finnish (NFE) AF: 0.290 AC: 19690 AN: 67998

Other (OTH) AF: 0.408 AC: 862 AN: 2114

Alfa AF: 0.322 Hom.: 4806

Bravo AF: 0.458

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		-0.30
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: rs6519520; hg19: chr22-24991895;