rs2006227

Variant names:

• chr22-24599789-C-A
• rs2006227
• ENST00000652248.1:n.*168-8165C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-24599789-C-A
• chr22-24599789-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000652248.1(ENSG00000286070):​n.*168-8165C>A 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 151,964 control chromosomes in the GnomAD database, including 11,461 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 (11461 hom., cov: 33)
• Consequence: ENSG00000286070 ENST00000652248.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 4 publications found

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]

GGT1 Gene-Disease associations (from GenCC):

• gamma-glutamyl transpeptidase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000652248.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGT1	NM_013430.3		c.-428-8165C>A		intron	N/A	NP_038347.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286070	ENST00000652248.1		n.*168-8165C>A		intron	N/A	ENSP00000499210.1
	GGT1	ENST00000411974.5	TSL:3	c.-324+4903C>A		intron	N/A	ENSP00000389935.1
	GGT1	ENST00000456869.5	TSL:3	c.-432+4903C>A		intron	N/A	ENSP00000415129.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58382 AN: 151848 Hom.: 11456 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.384 AC: 58426 AN: 151964 Hom.: 11461 Cov.: 33 AF XY: 0.380 AC XY: 28244 AN XY: 74280

African (AFR) AF: 0.421 AC: 17439 AN: 41420

American (AMR) AF: 0.451 AC: 6894 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1529 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1903 AN: 5162

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4820

European-Finnish (FIN) AF: 0.318 AC: 3357 AN: 10554

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.364 AC: 24750 AN: 67950

Other (OTH) AF: 0.404 AC: 853 AN: 2112

Alfa AF: 0.261 Hom.: 732

Bravo AF: 0.399

Asia WGS AF: 0.338 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.023
DANN	Benign	0.55
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2006227; hg19: chr22-24995756;