rs5751902

Variant names:

• chr22-24600663-C-T
• rs5751902
• ENST00000652248.1:n.*168-7291C>T

Variant summary

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

The ENST00000652248.1(ENSG00000286070):​n.*168-7291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,194 control chromosomes in the GnomAD database, including 7,962 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 0.30 (7962 hom., cov: 34)
• Consequence: ENSG00000286070 ENST00000652248.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 16 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGT1	NM_013430.3	c.-428-7291C>T		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.*168-7291C>T		intron_variant	Intron 5 of 19			ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45364 AN: 152076 Hom.: 7959 Cov.: 34

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.298 AC: 45379 AN: 152194 Hom.: 7962 Cov.: 34 AF XY: 0.305 AC XY: 22728 AN XY: 74398

African (AFR) AF: 0.112 AC: 4660 AN: 41562

American (AMR) AF: 0.324 AC: 4959 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3472

East Asian (EAS) AF: 0.382 AC: 1979 AN: 5176

South Asian (SAS) AF: 0.408 AC: 1968 AN: 4824

European-Finnish (FIN) AF: 0.415 AC: 4397 AN: 10586

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25123 AN: 67964

Other (OTH) AF: 0.307 AC: 650 AN: 2116

Alfa AF: 0.339 Hom.: 32049

Bravo AF: 0.282

Asia WGS AF: 0.356 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-1.1
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: rs5751902; hg19: chr22-24996630;