rs17194931

chr8-63031785-G-Achr8-63031785-G-C

Variant summary

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

The NM_003878.3(GGH):c.225-1568C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 152,222 control chromosomes in the GnomAD database, including 437 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 0.071 (437 hom., cov: 32)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGH	NM_003878.3	c.225-1568C>T		intron_variant		ENST00000260118.7
GGH	NM_001410926.1	c.225-1568C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGH	ENST00000260118.7	c.225-1568C>T		intron_variant		1	NM_003878.3	P1

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10832 AN: 152104 Hom.: 435 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0771

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0946

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0712 AC: 10831 AN: 152222 Hom.: 437 Cov.: 32 AF XY: 0.0710 AC XY: 5281 AN XY: 74416

Gnomad4 AFR AF: 0.0274

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0749

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0588

Gnomad4 NFE AF: 0.0946

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0682 Hom.: 55

Bravo AF: 0.0676

Asia WGS AF: 0.114 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.0
Dann	Benign	0.50

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: rs17194931; hg19: chr8-63944344;