dbSNP rs11545078: GGH:p.Thr151Ile (chr8-63026205-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 NM_003878.3(GGH):c.452C>T(p.Thr151Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0959 in 1,607,800 control chromosomes in the GnomAD database, including 8,203 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 0.079 ( 482 hom., cov: 33)

Exomes 𝑓: 0.098 ( 7721 hom. )

Consequence

GGH
NM_003878.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.18

Publications

89 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 (MetaRNN=0.0017904639).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GGH	NM_003878.3 link	c.452C>T	p.Thr151Ile	missense_variant	Exon 5 of 9	ENST00000260118.7	NP_003869.1
GGH	NM_001410926.1 link	c.452C>T	p.Thr151Ile	missense_variant	Exon 5 of 8		NP_001397855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7 link	c.452C>T	p.Thr151Ile	missense_variant	Exon 5 of 9	1	NM_003878.3	ENSP00000260118.6

Frequencies

GnomAD3 genomes

AF:

0.0786

AC:

11963

AN:

152186

Hom.:

479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0529

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0538

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0747

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0589

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0947

Gnomad OTH

AF:

0.0785

GnomAD2 exomes

AF:

0.0878

AC:

21720

AN:

247448

AF XY:

0.0949

show subpopulations

Gnomad AFR exome

AF:

0.0524

Gnomad AMR exome

AF:

0.0349

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.0769

Gnomad FIN exome

AF:

0.0557

Gnomad NFE exome

AF:

0.0943

Gnomad OTH exome

AF:

0.0897

GnomAD4 exome

AF:

0.0977

AC:

142159

AN:

1455496

Hom.:

7721

Cov.:

AF XY:

0.100

AC XY:

72708

AN XY:

724150

show subpopulations

African (AFR)

AF:

0.0504

AC:

1677

AN:

33252

American (AMR)

AF:

0.0386

AC:

1708

AN:

44222

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

3126

AN:

26038

East Asian (EAS)

AF:

0.0711

AC:

2806

AN:

39438

South Asian (SAS)

AF:

0.167

AC:

14275

AN:

85244

European-Finnish (FIN)

AF:

0.0580

AC:

3096

AN:

53382

Middle Eastern (MID)

AF:

0.110

AC:

632

AN:

5762

European-Non Finnish (NFE)

AF:

0.0985

AC:

109134

AN:

1107994

Other (OTH)

AF:

0.0948

AC:

5705

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

5899

11799

17698

23598

29497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4076

8152

12228

16304

20380

<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:

0.0786

AC:

11976

AN:

152304

Hom.:

482

Cov.:

AF XY:

0.0784

AC XY:

5837

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0531

AC:

2208

AN:

41578

American (AMR)

AF:

0.0536

AC:

820

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

424

AN:

3468

East Asian (EAS)

AF:

0.0750

AC:

389

AN:

5184

South Asian (SAS)

AF:

0.167

AC:

808

AN:

4828

European-Finnish (FIN)

AF:

0.0589

AC:

625

AN:

10614

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0947

AC:

6442

AN:

68024

Other (OTH)

AF:

0.0777

AC:

164

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

590

1181

1771

2362

2952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<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:

0.0909

Hom.:

2809

Bravo

AF:

0.0765

TwinsUK

AF:

0.108

AC:

399

ALSPAC

AF:

0.101

AC:

390

ESP6500AA

AF:

0.0601

AC:

265

ESP6500EA

AF:

0.0960

AC:

826

ExAC

AF:

0.0935

AC:

11355

Asia WGS

AF:

0.117

AC:

413

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

4.2

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.19

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.028

Polyphen

0.63

Vest4

0.094

MPC

0.12

ClinPred

0.034

GERP RS

5.9

PromoterAI

0.0091

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.82

Mutation Taster

=77/23

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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