rs8135987

Variant names:

• chr22-24616887-T-C
• rs8135987
• NM_001288833.2:c.382+1760T>C

Variant summary

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

The NM_001288833.2(GGT1):​c.382+1760T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,900 control chromosomes in the GnomAD database, including 11,670 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 0.38 (11670 hom., cov: 31)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.731
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGT1	NM_001288833.2	c.382+1760T>C		intron_variant	Intron 7 of 15	ENST00000400382.6	NP_001275762.1
GGT1	NM_013421.3	c.382+1760T>C		intron_variant	Intron 8 of 16		NP_038265.2
GGT1	NM_013430.3	c.382+1760T>C		intron_variant	Intron 7 of 15		NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6	c.382+1760T>C		intron_variant	Intron 7 of 15	2	NM_001288833.2	ENSP00000383232.1
ENSG00000286070	ENST00000652248.1	n.*872+1760T>C		intron_variant	Intron 11 of 19			ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58381 AN: 151782 Hom.: 11646 Cov.: 31

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.385 AC: 58452 AN: 151900 Hom.: 11670 Cov.: 31 AF XY: 0.382 AC XY: 28346 AN XY: 74250

African (AFR) AF: 0.488 AC: 20207 AN: 41388

American (AMR) AF: 0.427 AC: 6511 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1489 AN: 3464

East Asian (EAS) AF: 0.298 AC: 1539 AN: 5158

South Asian (SAS) AF: 0.297 AC: 1427 AN: 4812

European-Finnish (FIN) AF: 0.309 AC: 3272 AN: 10572

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22795 AN: 67936

Other (OTH) AF: 0.387 AC: 816 AN: 2108

Alfa AF: 0.370 Hom.: 1303

Bravo AF: 0.401

Asia WGS AF: 0.314 AC: 1091 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	7.4
DANN	Benign	0.50
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs8135987; hg19: chr22-25012854;