22-24615365-A-G

Position:

• chr22-24615365-A-G

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+238A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,812 control chromosomes in the GnomAD database, including 18,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (18823 hom., cov: 32)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0190

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 22-24615365-A-G is Benign according to our data. Variant chr22-24615365-A-G is described in ClinVar as [Benign]. Clinvar id is 1290240.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	Protein	UniProt
GGT1	NM_001288833.2	c.382+238A>G		intron_variant		ENST00000400382.6	NP_001275762.1
GGT1	NM_013421.3	c.382+238A>G		intron_variant			NP_038265.2
GGT1	NM_013430.3	c.382+238A>G		intron_variant			NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6	c.382+238A>G		intron_variant		2	NM_001288833.2	ENSP00000383232.1
ENSG00000286070	ENST00000652248.1	n.*872+238A>G		intron_variant				ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69520 AN: 151692 Hom.: 18778 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.459 AC: 69625 AN: 151812 Hom.: 18823 Cov.: 32 AF XY: 0.453 AC XY: 33597 AN XY: 74220

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.444

Alfa AF: 0.207 Hom.: 393

Bravo AF: 0.487

Asia WGS AF: 0.348 AC: 1210 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	-0.84
CADD	Benign	1.4
DANN	Benign	0.59

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: rs389004; hg19: chr22-25011332;