chr7-30501416-G-A

Position:

• chr7-30501416-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024051.4(GGCT):​c.142-735C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,022 control chromosomes in the GnomAD database, including 20,527 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 0.47 (20527 hom., cov: 32)
• Consequence: GGCT NM_024051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGCT	NM_024051.4	c.142-735C>T		intron_variant		ENST00000275428.9	NP_076956.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGCT	ENST00000275428.9	c.142-735C>T		intron_variant		1	NM_024051.4	ENSP00000275428.4
ENSG00000281039	ENST00000598361.4	c.-114-735C>T		intron_variant		5		ENSP00000470615.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71684 AN: 151904 Hom.: 20525 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.472 AC: 71690 AN: 152022 Hom.: 20527 Cov.: 32 AF XY: 0.470 AC XY: 34939 AN XY: 74276

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.495

Alfa AF: 0.597 Hom.: 27093

Bravo AF: 0.448

Asia WGS AF: 0.384 AC: 1336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs2391870; hg19: chr7-30541032; COSMIC: COSV50040930; COSMIC: COSV50040930;