22-24614976-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.296-65T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 137,996 control chromosomes in the GnomAD database, including 3,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (3066 hom., cov: 31)
  • Exomes 𝑓: 0.021 (2703 hom.)
  • Failed GnomAD Quality Control
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.17

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=-0.98).
• BP6: Variant 22-24614976-T-C is Benign according to our data. Variant chr22-24614976-T-C is described in ClinVar as [Benign]. Clinvar id is 1289175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGT1	NM_001288833.2	c.296-65T>C		intron_variant		ENST00000400382.6
GGT1	NM_013421.3	c.296-65T>C		intron_variant
GGT1	NM_013430.3	c.296-65T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGT1	ENST00000400382.6	c.296-65T>C		intron_variant		2	NM_001288833.2	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 16945 AN: 137880 Hom.: 3048 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.00962

Gnomad EAS AF: 0.000262

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.000623

Gnomad MID AF: 0.0325

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.0882

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0211 AC: 18498 AN: 877812 Hom.: 2703 Cov.: 24 AF XY: 0.0189 AC XY: 8453 AN XY: 447926

Gnomad4 AFR exome AF: 0.467

Gnomad4 AMR exome AF: 0.0286

Gnomad4 ASJ exome AF: 0.0107

Gnomad4 EAS exome AF: 0.0000605

Gnomad4 SAS exome AF: 0.0228

Gnomad4 FIN exome AF: 0.000497

Gnomad4 NFE exome AF: 0.00145

Gnomad4 OTH exome AF: 0.0477

GnomAD4 genome AF: 0.123 AC: 16999 AN: 137996 Hom.: 3066 Cov.: 31 AF XY: 0.119 AC XY: 7955 AN XY: 66628

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.00962

Gnomad4 EAS AF: 0.000262

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.000623

Gnomad4 NFE AF: 0.00179

Gnomad4 OTH AF: 0.0867

Alfa AF: 0.105 Hom.: 218

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 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.037
Dann	Benign	0.12

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: rs7284160; hg19: chr22-25010943; COSMIC: COSV50643551; COSMIC: COSV50643551;