chr7-30500783-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024051.4(GGCT):​c.142-102C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000427 in 702,482 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGCT	NM_024051.4	MANE Select	c.142-102C>G		intron	N/A	NP_076956.1
	GGCT	NM_001199815.2		c.142-102C>G		intron	N/A	NP_001186744.1
	GGCT	NM_001199816.2		c.142-102C>G		intron	N/A	NP_001186745.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000427 AC: 3 AN: 702482 Hom.: 0 AF XY: 0.00000275 AC XY: 1 AN XY: 363732

African (AFR) AF: 0.00 AC: 0 AN: 17356

American (AMR) AF: 0.0000413 AC: 1 AN: 24188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16354

East Asian (EAS) AF: 0.00 AC: 0 AN: 33788

South Asian (SAS) AF: 0.00 AC: 0 AN: 52802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2554

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 479090

Other (OTH) AF: 0.0000585 AC: 2 AN: 34188

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 17612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.4
DANN	Benign	0.81
PhyloP100		-0.83

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;