rs3824333

Variant names:

• chr8-63028658-T-C
• rs3824333
• NM_003878.3:c.276-1393A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003878.3(GGH):​c.276-1393A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,064 control chromosomes in the GnomAD database, including 1,388 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 0.12 (1388 hom., cov: 32)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 1 publications found

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]

ENSG00000310188 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGH	NM_003878.3	c.276-1393A>G		intron_variant	Intron 3 of 8	ENST00000260118.7	NP_003869.1
GGH	NM_001410926.1	c.276-1393A>G		intron_variant	Intron 3 of 7		NP_001397855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7	c.276-1393A>G		intron_variant	Intron 3 of 8	1	NM_003878.3	ENSP00000260118.6

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18932 AN: 151946 Hom.: 1378 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.125 AC: 18951 AN: 152064 Hom.: 1388 Cov.: 32 AF XY: 0.130 AC XY: 9645 AN XY: 74314

African (AFR) AF: 0.123 AC: 5087 AN: 41494

American (AMR) AF: 0.175 AC: 2663 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1759 AN: 5158

South Asian (SAS) AF: 0.132 AC: 634 AN: 4820

European-Finnish (FIN) AF: 0.149 AC: 1574 AN: 10572

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0949 AC: 6454 AN: 67980

Other (OTH) AF: 0.117 AC: 247 AN: 2112

Alfa AF: 0.114 Hom.: 153

Bravo AF: 0.128

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.35
PhyloP100		-0.038
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3824333; hg19: chr8-63941217;