rs5751901

chr22-24596299-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013430.3(GGT1):c.-428-11655T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,090 control chromosomes in the GnomAD database, including 11,362 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11362 hom., cov: 32)
• Consequence: GGT1 NM_013430.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGT1	NM_013430.3	c.-428-11655T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGT1	ENST00000411974.5	c.-324+1413T>C		intron_variant		3
GGT1	ENST00000456869.5	c.-432+1413T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58374 AN: 151972 Hom.: 11355 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.384 AC: 58416 AN: 152090 Hom.: 11362 Cov.: 32 AF XY: 0.380 AC XY: 28236 AN XY: 74368

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.406

Alfa AF: 0.377 Hom.: 20242

Bravo AF: 0.400

Asia WGS AF: 0.342 AC: 1187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.36
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: rs5751901; hg19: chr22-24992266;