8-63028217-T-A

Position:

• chr8-63028217-T-A

Variant summary

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

The NM_003878.3(GGH):​c.276-952A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,896 control chromosomes in the GnomAD database, including 3,447 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 (3447 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GGH NM_003878.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGH	NM_003878.3	c.276-952A>T		intron_variant		ENST00000260118.7	NP_003869.1
GGH	NM_001410926.1	c.276-952A>T		intron_variant			NP_001397855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7	c.276-952A>T		intron_variant		1	NM_003878.3	ENSP00000260118	P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30672 AN: 151776 Hom.: 3447 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.264

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.202 AC: 30685 AN: 151896 Hom.: 3447 Cov.: 31 AF XY: 0.204 AC XY: 15130 AN XY: 74222

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.263

Alfa AF: 0.0911 Hom.: 128

Bravo AF: 0.219

Asia WGS AF: 0.306 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3780130; hg19: chr8-63940776;