Genetic Variant NM_024051.4:c.142-102C>A (chr7-30500783-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024051.4(GGCT):c.142-102C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 852,898 control chromosomes in the GnomAD database, including 206,270 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 0.67 ( 34094 hom., cov: 33)

Exomes 𝑓: 0.70 ( 172176 hom. )

Consequence

GGCT
NM_024051.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.835

Publications

9 publications found

Variant links:

Genes affected

GGCT (HGNC:21705): (gamma-glutamylcyclotransferase) The protein encoded by this gene catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides, the penultimate step in glutathione catabolism, and may play a critical role in glutathione homeostasis. The encoded protein may also play a role in cell proliferation, and the expression of this gene is a potential marker for cancer. Pseudogenes of this gene are located on the long arm of chromosome 5 and the short arm of chromosomes 2 and 20. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

GGCT links:

ENSG00000281039 (HGNC:):

ENSG00000281039 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGCT	NM_024051.4 link	c.142-102C>A		intron_variant	Intron 1 of 3	ENST00000275428.9	NP_076956.1	O75223-1A0A090N7V5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGCT	ENST00000275428.9 link	c.142-102C>A		intron_variant	Intron 1 of 3	1	NM_024051.4	ENSP00000275428.4		O75223-1
ENSG00000281039	ENST00000598361.4 link	c.-114-102C>A		intron_variant	Intron 2 of 4	5		ENSP00000470615.1		M0QZK8

Frequencies

GnomAD3 genomes

AF:

0.666

AC:

101303

AN:

152022

Hom.:

34078

Cov.:

show subpopulations

Gnomad AFR

AF:

0.582

Gnomad AMI

AF:

0.623

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.765

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.705

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.693

GnomAD4 exome

AF:

0.697

AC:

488752

AN:

700758

Hom.:

172176

AF XY:

0.694

AC XY:

251763

AN XY:

362866

show subpopulations

African (AFR)

AF:

0.571

AC:

9873

AN:

17302

American (AMR)

AF:

0.603

AC:

14555

AN:

24118

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

12333

AN:

16320

East Asian (EAS)

AF:

0.654

AC:

22087

AN:

33750

South Asian (SAS)

AF:

0.590

AC:

31050

AN:

52664

European-Finnish (FIN)

AF:

0.701

AC:

29479

AN:

42078

Middle Eastern (MID)

AF:

0.694

AC:

1765

AN:

2544

European-Non Finnish (NFE)

AF:

0.720

AC:

343811

AN:

477836

Other (OTH)

AF:

0.697

AC:

23799

AN:

34146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7011

14022

21034

28045

35056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5566

11132

16698

22264

27830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.666

AC:

101350

AN:

152140

Hom.:

34094

Cov.:

AF XY:

0.664

AC XY:

49354

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.582

AC:

24122

AN:

41470

American (AMR)

AF:

0.634

AC:

9705

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.765

AC:

2655

AN:

3470

East Asian (EAS)

AF:

0.677

AC:

3509

AN:

5182

South Asian (SAS)

AF:

0.601

AC:

2900

AN:

4822

European-Finnish (FIN)

AF:

0.705

AC:

7451

AN:

10574

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.717

AC:

48759

AN:

67996

Other (OTH)

AF:

0.694

AC:

1468

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1772

3543

5315

7086

8858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.687

Hom.:

17612

Bravo

AF:

0.658

Asia WGS

AF:

0.640

AC:

2225

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.3

(source)

DANN

Benign

0.79

PhyloP100

-0.83

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over