rs5751902

Positions:

• chr22-24600663-C-T

Variant summary

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

The NM_013430.3(GGT1):​c.-428-7291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,194 control chromosomes in the GnomAD database, including 7,962 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 0.30 (7962 hom., cov: 34)
• Consequence: GGT1 NM_013430.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

ENSG00000286070 (HGNC:):

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGT1	NM_013430.3	c.-428-7291C>T		intron_variant			NP_038347.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000286070	ENST00000652248.1	n.*168-7291C>T		intron_variant				ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45364 AN: 152076 Hom.: 7959 Cov.: 34

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.298 AC: 45379 AN: 152194 Hom.: 7962 Cov.: 34 AF XY: 0.305 AC XY: 22728 AN XY: 74398

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.307

Alfa AF: 0.351 Hom.: 14180

Bravo AF: 0.282

Asia WGS AF: 0.356 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.69

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: rs5751902; hg19: chr22-24996630;