8-63025116-C-T

Variant summary

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

The NM_003878.3(GGH):c.500-930G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,152 control chromosomes in the GnomAD database, including 47,577 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 0.78 (47577 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63

Genes affected

GGH (HGNC:4248): (gamma-glutamyl hydrolase) This gene catalyzes the hydrolysis of folylpoly-gamma-glutamates and antifolylpoly-gamma-glutamates by the removal of gamma-linked polyglutamates and glutamate. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGH	NM_003878.3	c.500-930G>A		intron_variant		ENST00000260118.7
GGH	NM_001410926.1	c.500-930G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGH	ENST00000260118.7	c.500-930G>A		intron_variant		1	NM_003878.3	P1
	ENST00000521556.1	n.620+125C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118849 AN: 152032 Hom.: 47513 Cov.: 32

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.782 AC: 118972 AN: 152150 Hom.: 47577 Cov.: 32 AF XY: 0.786 AC XY: 58469 AN XY: 74358

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.786

Alfa AF: 0.730 Hom.: 4854

Bravo AF: 0.797

Asia WGS AF: 0.917 AC: 3189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.29
Dann	Benign	0.56

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: rs7010484; hg19: chr8-63937675; COSMIC: COSV52652031; COSMIC: COSV52652031;