8-63033214-T-C

Position:

• chr8-63033214-T-C

Variant summary

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

The NM_003878.3(GGH):​c.224+2442A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,310 control chromosomes in the GnomAD database, including 493 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 0.080 (493 hom., cov: 32)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00

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=-1.0).
• 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.224+2442A>G		intron_variant		ENST00000260118.7
GGH	NM_001410926.1	c.224+2442A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGH	ENST00000260118.7	c.224+2442A>G		intron_variant		1	NM_003878.3	P1

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12119 AN: 152192 Hom.: 490 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0744

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0590

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0797 AC: 12134 AN: 152310 Hom.: 493 Cov.: 32 AF XY: 0.0795 AC XY: 5921 AN XY: 74496

Gnomad4 AFR AF: 0.0568

Gnomad4 AMR AF: 0.0540

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0748

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0590

Gnomad4 NFE AF: 0.0947

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0857 Hom.: 112

Bravo AF: 0.0778

Asia WGS AF: 0.118 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.074
DANN	Benign	0.27

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: rs11990678; hg19: chr8-63945773;