chr22-24610949-T-C

Position:

• chr22-24610949-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.-7-126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 771,240 control chromosomes in the GnomAD database, including 10,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1313 hom., cov: 30)
  • Exomes 𝑓: 0.17 (8890 hom.)
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.927

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=-0.87).
• BP6: Variant 22-24610949-T-C is Benign according to our data. Variant chr22-24610949-T-C is described in ClinVar as [Benign]. Clinvar id is 1239221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGT1	NM_001288833.2	c.-7-126T>C		intron_variant		ENST00000400382.6	NP_001275762.1
GGT1	NM_013421.3	c.-7-126T>C		intron_variant			NP_038265.2
GGT1	NM_013430.3	c.-7-126T>C		intron_variant			NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6	c.-7-126T>C		intron_variant		2	NM_001288833.2	ENSP00000383232.1
ENSG00000286070	ENST00000652248.1	n.*484-126T>C		intron_variant				ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18711 AN: 151434 Hom.: 1309 Cov.: 30

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.165 AC: 102278 AN: 619686 Hom.: 8890 AF XY: 0.168 AC XY: 53949 AN XY: 321568

Gnomad4 AFR exome AF: 0.0307

Gnomad4 AMR exome AF: 0.0625

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.00590

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.163

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.123 AC: 18716 AN: 151554 Hom.: 1313 Cov.: 30 AF XY: 0.121 AC XY: 8986 AN XY: 74062

Gnomad4 AFR AF: 0.0337

Gnomad4 AMR AF: 0.0754

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.108

Alfa AF: 0.144 Hom.: 162

Bravo AF: 0.112

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 15, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.76

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: rs370160909; hg19: chr22-25006916;