Genetic Variant GGH:n.516T>G (chr8-63038892-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000677327.1(GGH):n.516T>G 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 0.247 in 487,604 control chromosomes in the GnomAD database, including 15,498 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 0.25 ( 4751 hom., cov: 33)

Exomes 𝑓: 0.25 ( 10747 hom. )

Consequence

GGH
ENST00000677327.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.180

Publications

13 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGH	NM_003878.3 link	c.-124T>G		upstream_gene_variant		ENST00000260118.7	NP_003869.1	Q92820
GGH	NM_001410926.1 link	c.-124T>G		upstream_gene_variant			NP_001397855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7 link	c.-124T>G		upstream_gene_variant		1	NM_003878.3	ENSP00000260118.6		Q92820

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37232

AN:

151920

Hom.:

4742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.202

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.247

AC:

83021

AN:

335572

Hom.:

10747

Cov.:

AF XY:

0.250

AC XY:

43872

AN XY:

175212

show subpopulations

African (AFR)

AF:

0.166

AC:

1353

AN:

8158

American (AMR)

AF:

0.234

AC:

2016

AN:

8628

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

2781

AN:

10146

East Asian (EAS)

AF:

0.213

AC:

4972

AN:

23314

South Asian (SAS)

AF:

0.239

AC:

4896

AN:

20474

European-Finnish (FIN)

AF:

0.243

AC:

5940

AN:

24446

Middle Eastern (MID)

AF:

0.225

AC:

337

AN:

1498

European-Non Finnish (NFE)

AF:

0.255

AC:

55871

AN:

219360

Other (OTH)

AF:

0.248

AC:

4855

AN:

19548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2730

5460

8190

10920

13650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

498

996

1494

1992

2490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.245

AC:

37265

AN:

152032

Hom.:

4751

Cov.:

AF XY:

0.245

AC XY:

18246

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.178

AC:

7391

AN:

41508

American (AMR)

AF:

0.236

AC:

3606

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

964

AN:

3464

East Asian (EAS)

AF:

0.203

AC:

1037

AN:

5118

South Asian (SAS)

AF:

0.300

AC:

1449

AN:

4830

European-Finnish (FIN)

AF:

0.257

AC:

2724

AN:

10596

Middle Eastern (MID)

AF:

0.243

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.282

AC:

19147

AN:

67920

Other (OTH)

AF:

0.269

AC:

566

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1444

2888

4332

5776

7220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.251

Hom.:

607

Bravo

AF:

0.242

Asia WGS

AF:

0.259

AC:

901

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.18

PromoterAI

0.039

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over