dbSNP rs3758149: GGH:n.239C>T (chr8-63039169-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000677327.1(GGH):n.239C>T 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 0.242 in 173,154 control chromosomes in the GnomAD database, including 5,249 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 0.24 ( 4751 hom., cov: 33)

Exomes 𝑓: 0.22 ( 498 hom. )

Consequence

GGH
ENST00000677327.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.450

Publications

64 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
GGH	ENST00000677327.1 link	n.239C>T	non_coding_transcript_exon_variant	Exon 1 of 8
GGH	ENST00000679326.1 link	n.-401C>T	non_coding_transcript_exon_variant	Exon 1 of 10	ENSP00000504262.1	A0A7I2YQQ3
GGH	ENST00000679326.1 link	n.-401C>T	5_prime_UTR_variant	Exon 1 of 10	ENSP00000504262.1	A0A7I2YQQ3

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37235

AN:

152038

Hom.:

4743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.220

AC:

4613

AN:

20998

Hom.:

498

Cov.:

AF XY:

0.217

AC XY:

2330

AN XY:

10744

show subpopulations

African (AFR)

AF:

0.127

AC:

114

AN:

898

American (AMR)

AF:

0.180

AC:

AN:

490

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

187

AN:

816

East Asian (EAS)

AF:

0.192

AC:

326

AN:

1702

South Asian (SAS)

AF:

0.194

AC:

AN:

180

European-Finnish (FIN)

AF:

0.223

AC:

331

AN:

1482

Middle Eastern (MID)

AF:

0.189

AC:

AN:

122

European-Non Finnish (NFE)

AF:

0.229

AC:

3173

AN:

13848

Other (OTH)

AF:

0.230

AC:

336

AN:

1460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

181

362

543

724

905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

37270

AN:

152156

Hom.:

4751

Cov.:

AF XY:

0.245

AC XY:

18242

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.178

AC:

7389

AN:

41530

American (AMR)

AF:

0.235

AC:

3599

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

968

AN:

3470

East Asian (EAS)

AF:

0.203

AC:

1048

AN:

5162

South Asian (SAS)

AF:

0.300

AC:

1446

AN:

4826

European-Finnish (FIN)

AF:

0.257

AC:

2724

AN:

10594

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.282

AC:

19149

AN:

67970

Other (OTH)

AF:

0.269

AC:

567

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1449

2898

4346

5795

7244

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:

0.269

Hom.:

8346

Bravo

AF:

0.242

Asia WGS

AF:

0.260

AC:

905

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.1

(source)

DANN

Benign

0.91

PhyloP100

-0.45

PromoterAI

-0.087

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