rs12681874

Positions:

• chr8-63029783-C-T

Variant summary

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

The NM_003878.3(GGH):​c.275+384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,592 control chromosomes in the GnomAD database, including 2,633 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 0.18 (2633 hom., cov: 31)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGH	NM_003878.3	c.275+384G>A		intron_variant		ENST00000260118.7
GGH	NM_001410926.1	c.275+384G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGH	ENST00000260118.7	c.275+384G>A		intron_variant		1	NM_003878.3	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27271 AN: 151474 Hom.: 2624 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.180 AC: 27302 AN: 151592 Hom.: 2633 Cov.: 31 AF XY: 0.184 AC XY: 13590 AN XY: 74040

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.168

Alfa AF: 0.164 Hom.: 262

Bravo AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs12681874; hg19: chr8-63942342;