rs719236

Positions:

• chr8-63039192-G-T

Variant summary

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

The ENST00000677327.1(GGH):​n.216C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 165,152 control chromosomes in the GnomAD database, including 1,044 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 0.11 (970 hom., cov: 33)
  • Exomes 𝑓: 0.10 (74 hom.)
• Consequence: GGH ENST00000677327.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000677327.1	n.216C>A		non_coding_transcript_exon_variant	1/8
GGH	ENST00000679326.1	c.-424C>A		5_prime_UTR_variant, NMD_transcript_variant	1/10			ENSP00000504262

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16072 AN: 152158 Hom.: 970 Cov.: 33

Gnomad AFR AF: 0.0895

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0882

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.103 AC: 1321 AN: 12876 Hom.: 74 Cov.: 0 AF XY: 0.103 AC XY: 680 AN XY: 6580

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.0800

Gnomad4 NFE exome AF: 0.0917

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.106 AC: 16076 AN: 152276 Hom.: 970 Cov.: 33 AF XY: 0.109 AC XY: 8117 AN XY: 74446

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.0928

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0883

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0925 Hom.: 88

Bravo AF: 0.113

Asia WGS AF: 0.157 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.5
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs719236; hg19: chr8-63951751;