chr22-24615000-G-C

Position:

• chr22-24615000-G-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.296-41G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 152,146 control chromosomes in the GnomAD database, including 841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (841 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (760 hom.)
  • Failed GnomAD Quality Control
• Consequence: GGT1 NM_001288833.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.366

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=-0.81).
• BP6: Variant 22-24615000-G-C is Benign according to our data. Variant chr22-24615000-G-C is described in ClinVar as [Benign]. Clinvar id is 1246179.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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGT1	NM_001288833.2	c.296-41G>C		intron_variant		ENST00000400382.6	NP_001275762.1
GGT1	NM_013421.3	c.296-41G>C		intron_variant			NP_038265.2
GGT1	NM_013430.3	c.296-41G>C		intron_variant			NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGT1	ENST00000400382.6	c.296-41G>C		intron_variant		2	NM_001288833.2	ENSP00000383232.1
ENSG00000286070	ENST00000652248.1	n.*786-41G>C		intron_variant				ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8800 AN: 152028 Hom.: 833 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0250

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.0471

GnomAD3 exomes AF: 0.0168 AC: 4067 AN: 242668 Hom.: 308 AF XY: 0.0143 AC XY: 1901 AN XY: 132658

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.000169

Gnomad SAS exome AF: 0.0213

Gnomad FIN exome AF: 0.0000933

Gnomad NFE exome AF: 0.000855

Gnomad OTH exome AF: 0.0105

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00735 AC: 10422 AN: 1417862 Hom.: 760 Cov.: 26 AF XY: 0.00703 AC XY: 4973 AN XY: 707544

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.0123

Gnomad4 ASJ exome AF: 0.000465

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.0202

Gnomad4 FIN exome AF: 0.000190

Gnomad4 NFE exome AF: 0.000484

Gnomad4 OTH exome AF: 0.0151

GnomAD4 genome AF: 0.0581 AC: 8836 AN: 152146 Hom.: 841 Cov.: 32 AF XY: 0.0564 AC XY: 4194 AN XY: 74416

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0249

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.000809

Gnomad4 OTH AF: 0.0461

Alfa AF: 0.00404 Hom.: 9

Bravo AF: 0.0651

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	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	-0.81
CADD	Benign	7.0
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs112952976; hg19: chr22-25010967;