22-24615353-T-C

Position:

• chr22-24615353-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001288833.2(GGT1):​c.382+226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,810 control chromosomes in the GnomAD database, including 18,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (18808 hom., cov: 31)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.21

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 22-24615353-T-C is Benign according to our data. Variant chr22-24615353-T-C is described in ClinVar as [Benign]. Clinvar id is 1236112.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGT1	NM_001288833.2	c.382+226T>C		intron_variant		ENST00000400382.6
GGT1	NM_013421.3	c.382+226T>C		intron_variant
GGT1	NM_013430.3	c.382+226T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGT1	ENST00000400382.6	c.382+226T>C		intron_variant		2	NM_001288833.2	P1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69450 AN: 151686 Hom.: 18762 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.458 AC: 69559 AN: 151810 Hom.: 18808 Cov.: 31 AF XY: 0.452 AC XY: 33574 AN XY: 74220

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.444

Alfa AF: 0.153 Hom.: 250

Bravo AF: 0.487

Asia WGS AF: 0.348 AC: 1207 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.079
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs28377326; hg19: chr22-25011320;