rs16930092

Positions:

• chr8-63027805-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.276-540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 152,030 control chromosomes in the GnomAD database, including 793 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 0.092 (793 hom., cov: 32)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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]

GGH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGH	NM_003878.3	c.276-540A>G		intron_variant		ENST00000260118.7	NP_003869.1
GGH	NM_001410926.1	c.276-540A>G		intron_variant			NP_001397855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7	c.276-540A>G		intron_variant		1	NM_003878.3	ENSP00000260118.6

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 14046 AN: 151910 Hom.: 791 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0962

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.0924 AC: 14052 AN: 152030 Hom.: 793 Cov.: 32 AF XY: 0.0912 AC XY: 6775 AN XY: 74324

Gnomad4 AFR AF: 0.0676

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0916

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.0978

Gnomad4 FIN AF: 0.0205

Gnomad4 NFE AF: 0.0962

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0869 Hom.: 75

Bravo AF: 0.103

Asia WGS AF: 0.149 AC: 514 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.35

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: rs16930092; hg19: chr8-63940364;