Variant 22-24614918-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001288833.2(GGT1):c.295+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,612,630 control chromosomes in the GnomAD database, including 1,560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 832 hom., cov: 31)

Exomes 𝑓: 0.0061 ( 728 hom. )

Consequence

GGT1
NM_001288833.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.927

Variant links:

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 links:

ENSG00000286070 (HGNC:):

ENSG00000286070 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 22-24614918-G-A is Benign according to our data. Variant chr22-24614918-G-A is described in ClinVar as [Benign]. Clinvar id is 1226346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GGT1	NM_001288833.2 linkuse as main transcript	c.295+12G>A	intron_variant	ENST00000400382.6	NP_001275762.1	P19440-1A0A140VJJ9
GGT1	NM_013421.3 linkuse as main transcript	c.295+12G>A	intron_variant		NP_038265.2	P19440-1A0A140VJJ9
GGT1	NM_013430.3 linkuse as main transcript	c.295+12G>A	intron_variant		NP_038347.2	P19440-1A0A140VJJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6 linkuse as main transcript	c.295+12G>A		intron_variant		2	NM_001288833.2	ENSP00000383232.1		P19440-1
ENSG00000286070	ENST00000652248.1 linkuse as main transcript	n.*785+12G>A		intron_variant				ENSP00000499210.1

Frequencies

GnomAD3 genomes

AF:

0.0572

AC:

8704

AN:

152050

Hom.:

824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0249

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.0469

GnomAD3 exomes

AF:

0.0141

AC:

3475

AN:

246346

Hom.:

300

AF XY:

0.0107

AC XY:

1441

AN XY:

134282

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000774

Gnomad OTH exome

AF:

0.00949

GnomAD4 exome

AF:

0.00606

AC:

8847

AN:

1460462

Hom.:

728

Cov.:

AF XY:

0.00522

AC XY:

3791

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.0122

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000510

Gnomad4 FIN exome

AF:

0.000188

Gnomad4 NFE exome

AF:

0.000472

Gnomad4 OTH exome

AF:

0.0135

GnomAD4 genome

AF:

0.0574

AC:

8742

AN:

152168

Hom.:

832

Cov.:

AF XY:

0.0553

AC XY:

4117

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.0248

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.0460

Alfa

AF:

0.0375

Hom.:

144

Bravo

AF:

0.0649

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.1

DANN

Benign

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over