chr22-24614974-G-A

Position:

• chr22-24614974-G-A

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.296-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,162 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (91 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (91 hom.)
  • Failed GnomAD Quality Control
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0570

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=-0.85).
• BP6: Variant 22-24614974-G-A is Benign according to our data. Variant chr22-24614974-G-A is described in ClinVar as [Benign]. Clinvar id is 1273127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGT1	NM_001288833.2	c.296-67G>A		intron_variant		ENST00000400382.6	NP_001275762.1
GGT1	NM_013421.3	c.296-67G>A		intron_variant			NP_038265.2
GGT1	NM_013430.3	c.296-67G>A		intron_variant			NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6	c.296-67G>A		intron_variant		2	NM_001288833.2	ENSP00000383232.1
ENSG00000286070	ENST00000652248.1	n.*786-67G>A		intron_variant				ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2976 AN: 152046 Hom.: 90 Cov.: 31

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00531

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0125

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00191 AC: 2720 AN: 1420370 Hom.: 91 Cov.: 26 AF XY: 0.00157 AC XY: 1113 AN XY: 708614

Gnomad4 AFR exome AF: 0.0701

Gnomad4 AMR exome AF: 0.00280

Gnomad4 ASJ exome AF: 0.0000387

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000211

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000502

Gnomad4 OTH exome AF: 0.00401

GnomAD4 genome AF: 0.0196 AC: 2988 AN: 152162 Hom.: 91 Cov.: 31 AF XY: 0.0183 AC XY: 1365 AN XY: 74402

Gnomad4 AFR AF: 0.0692

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0156 Hom.: 6

Bravo AF: 0.0224

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 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs143010532; hg19: chr22-25010941;