NM_003878.3:c.224+2442A>G

Variant names:

• chr8-63033214-T-C
• rs11990678
• NM_003878.3:c.224+2442A>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.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
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003878.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGH	NM_003878.3	MANE Select	c.224+2442A>G		intron	N/A	NP_003869.1
	GGH	NM_001410926.1		c.224+2442A>G		intron	N/A	NP_001397855.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGH	ENST00000260118.7	TSL:1 MANE Select	c.224+2442A>G		intron	N/A	ENSP00000260118.6
	GGH	ENST00000518113.2	TSL:3	c.224+2442A>G		intron	N/A	ENSP00000504520.1
	GGH	ENST00000677482.1		c.224+2442A>G		intron	N/A	ENSP00000504590.1

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

African (AFR) AF: 0.0568 AC: 2360 AN: 41570

American (AMR) AF: 0.0540 AC: 826 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3470

East Asian (EAS) AF: 0.0748 AC: 388 AN: 5188

South Asian (SAS) AF: 0.167 AC: 807 AN: 4822

European-Finnish (FIN) AF: 0.0590 AC: 627 AN: 10628

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0947 AC: 6440 AN: 68016

Other (OTH) AF: 0.0791 AC: 167 AN: 2110

Alfa AF: 0.0845 Hom.: 113

Bravo AF: 0.0778

Asia WGS AF: 0.118 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.074
DANN	Benign	0.27
PhyloP100		-3.0
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: rs11990678; hg19: chr8-63945773;