Genetic Variant GGH:n.286G>A (chr8-63039122-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000677327.1(GGH):n.286G>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 0.0000263 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GGH
ENST00000677327.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.151

Publications

24 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
GGH	ENST00000677327.1 link	n.286G>A	non_coding_transcript_exon_variant	Exon 1 of 8
GGH	ENST00000679326.1 link	n.-354G>A	non_coding_transcript_exon_variant	Exon 1 of 10	ENSP00000504262.1
GGH	ENST00000679326.1 link	n.-354G>A	5_prime_UTR_variant	Exon 1 of 10	ENSP00000504262.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

55146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

27856

African (AFR)

AF:

0.00

AC:

AN:

2038

American (AMR)

AF:

0.00

AC:

AN:

1482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2220

East Asian (EAS)

AF:

0.00

AC:

AN:

4798

South Asian (SAS)

AF:

0.00

AC:

AN:

572

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

35848

Other (OTH)

AF:

0.00

AC:

AN:

3886

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41584

American (AMR)

AF:

0.000261

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.4

(source)

DANN

Benign

0.82

PhyloP100

-0.15

PromoterAI

0.086

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over