rs2736676

Positions:

• chr8-63039417-C-T

Variant summary

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

The 8-63039417-C-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,178 control chromosomes in the GnomAD database, including 51,478 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 0.82 (51478 hom., cov: 32)
• Consequence: GGH ENST00000679326.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• 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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGH	ENST00000677327.1			upstream_gene_variant
GGH	ENST00000679326.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124323 AN: 152060 Hom.: 51411 Cov.: 32

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.818 AC: 124450 AN: 152178 Hom.: 51478 Cov.: 32 AF XY: 0.824 AC XY: 61297 AN XY: 74394

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.809

Alfa AF: 0.782 Hom.: 10374

Bravo AF: 0.824

Asia WGS AF: 0.924 AC: 3214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.15
DANN	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2736676; hg19: chr8-63951976;