rs1031552

chr8-63020631-G-Achr8-63020631-G-Cchr8-63020631-G-T

Variant summary

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

The NM_003878.3(GGH):c.698-3001C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,188 control chromosomes in the GnomAD database, including 1,385 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 0.12 (1385 hom., cov: 32)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGH	NM_003878.3	c.698-3001C>T		intron_variant		ENST00000260118.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGH	ENST00000260118.7	c.698-3001C>T		intron_variant		1	NM_003878.3	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18928 AN: 152070 Hom.: 1375 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.125 AC: 18948 AN: 152188 Hom.: 1385 Cov.: 32 AF XY: 0.130 AC XY: 9642 AN XY: 74392

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.0950

Gnomad4 OTH AF: 0.117

Alfa AF: 0.101 Hom.: 1528

Bravo AF: 0.128

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.68
Dann	Benign	0.44

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: rs1031552; hg19: chr8-63933190;