NM_003878.3:c.698-3001C>T

Variant names:

• chr8-63020631-G-A
• rs1031552
• NM_003878.3:c.698-3001C>T

Variant summary

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

The NM_003878.3(GGH):​c.698-3001C>T 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 152,188 control chromosomes in the GnomAD database, including 1,385 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 (1385 hom., cov: 32)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 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.698-3001C>T		intron	N/A	NP_003869.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GGH	ENST00000260118.7	TSL:1 MANE Select	c.698-3001C>T		intron	N/A	ENSP00000260118.6
	GGH	ENST00000677482.1		c.640-3001C>T		intron	N/A	ENSP00000504590.1
	GGH	ENST00000677919.1		c.184-3001C>T		intron	N/A	ENSP00000504579.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18928 AN: 152070 Hom.: 1375 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0570

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: 18948 AN: 152188 Hom.: 1385 Cov.: 32 AF XY: 0.130 AC XY: 9642 AN XY: 74392

African (AFR) AF: 0.123 AC: 5088 AN: 41516

American (AMR) AF: 0.174 AC: 2653 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3472

East Asian (EAS) AF: 0.340 AC: 1756 AN: 5160

South Asian (SAS) AF: 0.132 AC: 635 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1574 AN: 10600

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0950 AC: 6460 AN: 68018

Other (OTH) AF: 0.117 AC: 248 AN: 2114

Alfa AF: 0.105 Hom.: 3814

Bravo AF: 0.128

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.68
DANN	Benign	0.44
PhyloP100		-0.085
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: rs1031552; hg19: chr8-63933190;