Genetic Variant GGT1:c.165-145delA (chr22-24614614-CA-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001288833.2(GGT1):c.165-145delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 68,550 control chromosomes in the GnomAD database, including 500 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 500 hom., cov: 29)

Consequence

GGT1
NM_001288833.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.27

Publications

1 publications found

Variant links:

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

GGT1 links:

ENSG00000286070 (HGNC:):

ENSG00000286070 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 22-24614614-CA-C is Benign according to our data. Variant chr22-24614614-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1294465.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GGT1	NM_001288833.2	MANE Select	c.165-145delA	intron	N/A	NP_001275762.1	P19440-1
GGT1	NM_013421.3		c.165-145delA	intron	N/A	NP_038265.2	A0A140VJJ9
GGT1	NM_013430.3		c.165-145delA	intron	N/A	NP_038347.2	P19440-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GGT1	ENST00000400382.6	TSL:2 MANE Select	c.165-161delA	intron	N/A	ENSP00000383232.1	P19440-1
GGT1	ENST00000400380.5	TSL:1	c.165-161delA	intron	N/A	ENSP00000383231.1	P19440-1
ENSG00000286070	ENST00000652248.1		n.*655-161delA	intron	N/A	ENSP00000499210.1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

7482

AN:

68534

Hom.:

499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0747

Gnomad ASJ

AF:

0.0310

Gnomad EAS

AF:

0.0189

Gnomad SAS

AF:

0.0594

Gnomad FIN

AF:

0.00413

Gnomad MID

AF:

0.0610

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.0962

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

GnomAD4 genome

AF:

0.109

AC:

7493

AN:

68550

Hom.:

500

Cov.:

AF XY:

0.109

AC XY:

3489

AN XY:

32136

show subpopulations

African (AFR)

AF:

0.264

AC:

6389

AN:

24162

American (AMR)

AF:

0.0745

AC:

435

AN:

5840

Ashkenazi Jewish (ASJ)

AF:

0.0310

AC:

AN:

1712

East Asian (EAS)

AF:

0.0190

AC:

AN:

2052

South Asian (SAS)

AF:

0.0605

AC:

112

AN:

1852

European-Finnish (FIN)

AF:

0.00413

AC:

AN:

2420

Middle Eastern (MID)

AF:

0.0625

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0125

AC:

363

AN:

29154

Other (OTH)

AF:

0.0956

AC:

AN:

910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

237

474

711

948

1185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over