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 ENST00000679326.1(GGH):n.-401C>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
ENST00000679326.1 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000679326.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
GGH	ENST00000677327.1	n.239C>T	non_coding_transcript_exon	Exon 1 of 8
GGH	ENST00000679326.1	n.-401C>T	non_coding_transcript_exon	Exon 1 of 10	ENSP00000504262.1	A0A7I2YQQ3
GGH	ENST00000679326.1	n.-401C>T	5_prime_UTR	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over