Genetic Variant ENST00000677327.1:n.216C>A (chr8-63039192-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000677327.1(GGH):n.216C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 165,152 control chromosomes in the GnomAD database, including 1,044 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 0.11 ( 970 hom., cov: 33)

Exomes 𝑓: 0.10 ( 74 hom. )

Consequence

GGH
ENST00000677327.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.225

Variant links:

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]

GGH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
GGH	ENST00000677327.1 link	n.216C>A	non_coding_transcript_exon_variant	Exon 1 of 8
GGH	ENST00000679326.1 link	n.-424C>A	non_coding_transcript_exon_variant	Exon 1 of 10	ENSP00000504262.1	A0A7I2YQQ3
GGH	ENST00000679326.1 link	n.-424C>A	5_prime_UTR_variant	Exon 1 of 10	ENSP00000504262.1	A0A7I2YQQ3

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16072

AN:

152158

Hom.:

970

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0895

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.0923

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.0882

Gnomad OTH

AF:

0.130

GnomAD4 exome

AF:

0.103

AC:

1321

AN:

12876

Hom.:

Cov.:

AF XY:

0.103

AC XY:

680

AN XY:

6580

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.188

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.0800

Gnomad4 NFE exome

AF:

0.0917

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.106

AC:

16076

AN:

152276

Hom.:

970

Cov.:

AF XY:

0.109

AC XY:

8117

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0894

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.214

Gnomad4 SAS

AF:

0.0928

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.0883

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0925

Hom.:

Bravo

AF:

0.113

Asia WGS

AF:

0.157

AC:

543

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.5

DANN

Benign

0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over