chr22-24620239-A-G

Position:

• chr22-24620239-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001288833.2(GGT1):​c.383-89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 1,369,290 control chromosomes in the GnomAD database, including 13,401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2308 hom., cov: 29)
  • Exomes 𝑓: 0.076 (11093 hom.)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.167

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 -16 ACMG points.

• BP6: Variant 22-24620239-A-G is Benign according to our data. Variant chr22-24620239-A-G is described in ClinVar as [Benign]. Clinvar id is 1230205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGT1	NM_001288833.2	c.383-89A>G		intron_variant		ENST00000400382.6	NP_001275762.1
GGT1	NM_013421.3	c.383-89A>G		intron_variant			NP_038265.2
GGT1	NM_013430.3	c.383-89A>G		intron_variant			NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6	c.383-89A>G		intron_variant		2	NM_001288833.2	ENSP00000383232.1
ENSG00000286070	ENST00000652248.1	n.*873-89A>G		intron_variant				ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 21540 AN: 141900 Hom.: 2305 Cov.: 29

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.0820

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: 0.247

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.0760 AC: 93289 AN: 1227286 Hom.: 11093 AF XY: 0.0809 AC XY: 49040 AN XY: 606546

Gnomad4 AFR exome AF: 0.0200

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.0585

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.152 AC: 21542 AN: 142004 Hom.: 2308 Cov.: 29 AF XY: 0.149 AC XY: 10294 AN XY: 69228

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.261

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: 0.169

Alfa AF: 0.213 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	-0.83
CADD	Benign	2.3
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.66		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.66		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3865652; hg19: chr22-25016206; COSMIC: COSV50638195; COSMIC: COSV50638195;