8-63030158-C-T

Variant names:

• chr8-63030158-C-T
• rs4617146
• NM_003878.3:c.275+9G>A

Variant summary

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

The NM_003878.3(GGH):​c.275+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,302,010 control chromosomes in the GnomAD database, including 26,615 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 0.20 (3467 hom., cov: 32)
  • Exomes 𝑓: 0.19 (23148 hom.)
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGH	NM_003878.3	c.275+9G>A		intron_variant	Intron 3 of 8	ENST00000260118.7	NP_003869.1
GGH	NM_001410926.1	c.275+9G>A		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.275+9G>A		intron_variant	Intron 3 of 8	1	NM_003878.3	ENSP00000260118.6

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30765 AN: 151934 Hom.: 3467 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.263

GnomAD3 exomes AF: 0.228 AC: 56972 AN: 249336 Hom.: 7586 AF XY: 0.223 AC XY: 30096 AN XY: 134890

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.421

Gnomad SAS exome AF: 0.185

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.188 AC: 216748 AN: 1149960 Hom.: 23148 Cov.: 16 AF XY: 0.189 AC XY: 111215 AN XY: 587228

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.422

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.202 AC: 30777 AN: 152050 Hom.: 3467 Cov.: 32 AF XY: 0.204 AC XY: 15181 AN XY: 74306

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.262

Alfa AF: 0.206 Hom.: 5580

Bravo AF: 0.219

Asia WGS AF: 0.305 AC: 1054 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.9
DANN	Benign	0.80

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: rs4617146; hg19: chr8-63942717; COSMIC: COSV52649670; COSMIC: COSV52649670;