chr8-63037353-G-A

Position:

• chr8-63037353-G-A

Variant summary

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

The NM_003878.3(GGH):​c.109+1307C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,818 control chromosomes in the GnomAD database, including 15,743 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 0.45 (15743 hom., cov: 30)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GGH	NM_003878.3	c.109+1307C>T		intron_variant		ENST00000260118.7
GGH	NM_001410926.1	c.109+1307C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GGH	ENST00000260118.7	c.109+1307C>T		intron_variant		1	NM_003878.3	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67901 AN: 151698 Hom.: 15718 Cov.: 30

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.448 AC: 67968 AN: 151818 Hom.: 15743 Cov.: 30 AF XY: 0.450 AC XY: 33386 AN XY: 74170

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.464

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.438

Alfa AF: 0.396 Hom.: 16481

Bravo AF: 0.448

Asia WGS AF: 0.440 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.81

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: rs3780126; hg19: chr8-63949912;