rs719235

Positions:

• chr8-63039122-C-A
• chr8-63039122-C-T

Variant summary

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

The ENST00000677327.1(GGH):​n.286G>T 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 0.229 in 207,172 control chromosomes in the GnomAD database, including 6,592 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 0.21 (4389 hom., cov: 33)
  • Exomes 𝑓: 0.27 (2203 hom.)
• Consequence: GGH ENST00000677327.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 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.286G>T		non_coding_transcript_exon_variant	1/8
GGH	ENST00000679326.1	c.-354G>T		5_prime_UTR_variant, NMD_transcript_variant	1/10			ENSP00000504262

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32479 AN: 152062 Hom.: 4382 Cov.: 33

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.212

GnomAD4 exome AF: 0.273 AC: 15005 AN: 54992 Hom.: 2203 Cov.: 0 AF XY: 0.276 AC XY: 7657 AN XY: 27792

Gnomad4 AFR exome AF: 0.0505

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.213 AC: 32489 AN: 152180 Hom.: 4389 Cov.: 33 AF XY: 0.216 AC XY: 16056 AN XY: 74394

Gnomad4 AFR AF: 0.0555

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.220

Alfa AF: 0.252 Hom.: 894

Bravo AF: 0.190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.3
DANN	Benign	0.54

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: rs719235; hg19: chr8-63951681;