22-24620240-T-C

Position:

• chr22-24620240-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001288833.2(GGT1):​c.383-88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 1,358,472 control chromosomes in the GnomAD database, including 13,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2316 hom., cov: 29)
  • Exomes 𝑓: 0.077 (11103 hom.)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.40

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]

ENSG00000286070 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 22-24620240-T-C is Benign according to our data. Variant chr22-24620240-T-C is described in ClinVar as [Benign]. Clinvar id is 1183246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGT1	NM_001288833.2	c.383-88T>C		intron_variant		ENST00000400382.6	NP_001275762.1
GGT1	NM_013421.3	c.383-88T>C		intron_variant			NP_038265.2
GGT1	NM_013430.3	c.383-88T>C		intron_variant			NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6	c.383-88T>C		intron_variant		2	NM_001288833.2	ENSP00000383232.1
ENSG00000286070	ENST00000652248.1	n.*873-88T>C		intron_variant				ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 21513 AN: 141698 Hom.: 2313 Cov.: 29

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.0810

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.0768 AC: 93424 AN: 1216674 Hom.: 11103 AF XY: 0.0816 AC XY: 49091 AN XY: 601350

Gnomad4 AFR exome AF: 0.0200

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.0592

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.152 AC: 21515 AN: 141798 Hom.: 2316 Cov.: 29 AF XY: 0.149 AC XY: 10275 AN XY: 69120

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.166

Alfa AF: 0.207 Hom.: 329

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.94
CADD	Benign	0.15
DANN	Benign	0.25

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: rs3865651; hg19: chr22-25016207; COSMIC: COSV50638198; COSMIC: COSV50638198;