rs4049881

Variant names:

• chr22-24614779-T-C
• rs4049881
• NM_001288833.2:c.168T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001288833.2(GGT1):​c.168T>C​(p.Asp56Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,613,382 control chromosomes in the GnomAD database, including 1,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (686 hom., cov: 31)
  • Exomes 𝑓: 0.0067 (642 hom.)
• Consequence: GGT1 NM_001288833.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.56
• Publications: 6 publications found

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]

GGT1 Gene-Disease associations (from GenCC):

• gamma-glutamyl transpeptidase deficiency

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

ENSG00000286070 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 22-24614779-T-C is Benign according to our data. Variant chr22-24614779-T-C is described in ClinVar as Benign. ClinVar VariationId is 1244940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288833.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGT1	NM_001288833.2	MANE Select	c.168T>C	p.Asp56Asp	synonymous	Exon 6 of 16	NP_001275762.1	P19440-1
	GGT1	NM_013421.3		c.168T>C	p.Asp56Asp	synonymous	Exon 7 of 17	NP_038265.2	A0A140VJJ9
	GGT1	NM_013430.3		c.168T>C	p.Asp56Asp	synonymous	Exon 6 of 16	NP_038347.2	P19440-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGT1	ENST00000400382.6	TSL:2 MANE Select	c.168T>C	p.Asp56Asp	synonymous	Exon 6 of 16	ENSP00000383232.1	P19440-1
	GGT1	ENST00000400380.5	TSL:1	c.168T>C	p.Asp56Asp	synonymous	Exon 7 of 17	ENSP00000383231.1	P19440-1
	ENSG00000286070	ENST00000652248.1		n.*658T>C		non_coding_transcript_exon	Exon 10 of 20	ENSP00000499210.1

Frequencies

GnomAD3 genomes AF: 0.0527 AC: 8013 AN: 152026 Hom.: 678 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000765

Gnomad OTH AF: 0.0427

GnomAD2 exomes AF: 0.0153 AC: 3797 AN: 247736 AF XY: 0.0132

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.00975

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.000168

Gnomad FIN exome AF: 0.0000928

Gnomad NFE exome AF: 0.000757

Gnomad OTH exome AF: 0.00997

GnomAD4 exome AF: 0.00671 AC: 9807 AN: 1461238 Hom.: 642 Cov.: 32 AF XY: 0.00648 AC XY: 4711 AN XY: 726932

African (AFR) AF: 0.184 AC: 6141 AN: 33412

American (AMR) AF: 0.0113 AC: 505 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0201 AC: 1734 AN: 86240

European-Finnish (FIN) AF: 0.000188 AC: 10 AN: 53308

Middle Eastern (MID) AF: 0.00866 AC: 49 AN: 5658

European-Non Finnish (NFE) AF: 0.000449 AC: 499 AN: 1111750

Other (OTH) AF: 0.0143 AC: 860 AN: 60340

GnomAD4 genome AF: 0.0529 AC: 8045 AN: 152144 Hom.: 686 Cov.: 31 AF XY: 0.0513 AC XY: 3813 AN XY: 74388

African (AFR) AF: 0.179 AC: 7425 AN: 41466

American (AMR) AF: 0.0237 AC: 362 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0223 AC: 107 AN: 4806

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000765 AC: 52 AN: 68010

Other (OTH) AF: 0.0417 AC: 88 AN: 2108

Alfa AF: 0.0239 Hom.: 206

Bravo AF: 0.0593

EpiCase AF: 0.00120

EpiControl AF: 0.00101

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.078
DANN	Benign	0.45
PhyloP100		-2.6
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: rs4049881; hg19: chr22-25010746; COSMIC: COSV50638436; COSMIC: COSV50638436;