7-30500783-G-T

Variant names:

• chr7-30500783-G-T
• rs38410
• NM_024051.4:c.142-102C>A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835
• Publications: 9 publications found

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]

ENSG00000281039 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024051.4. 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
	GGCT	NM_024051.4	MANE Select	c.142-102C>A		intron	N/A	NP_076956.1	O75223-1
	GGCT	NM_001199815.2		c.142-102C>A		intron	N/A	NP_001186744.1	O75223-4
	GGCT	NM_001199816.2		c.142-102C>A		intron	N/A	NP_001186745.1	O75223-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGCT	ENST00000275428.9	TSL:1 MANE Select	c.142-102C>A		intron	N/A	ENSP00000275428.4	O75223-1
	GGCT	ENST00000005374.10	TSL:1	c.142-102C>A		intron	N/A	ENSP00000005374.6	O75223-2
	ENSG00000281039	ENST00000598361.4	TSL:5	c.-114-102C>A		intron	N/A	ENSP00000470615.1	M0QZK8

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101303 AN: 152022 Hom.: 34078 Cov.: 33

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

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

GnomAD4 genome AF: 0.666 AC: 101350 AN: 152140 Hom.: 34094 Cov.: 33 AF XY: 0.664 AC XY: 49354 AN XY: 74370

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.3
DANN	Benign	0.79
PhyloP100		-0.83
Mutation Taster		=98/2	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: rs38410; hg19: chr7-30540399; COSMIC: COSV50040900; COSMIC: COSV50040900;