Variant rs11786893 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The ENST00000260118.7(GGH):c.174G>A(p.Ala58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,613,068 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 5 hom., cov: 32)

Exomes 𝑓: 0.014 ( 167 hom. )

Consequence

GGH
ENST00000260118.7 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.23

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 8-63035706-C-T is Benign according to our data. Variant chr8-63035706-C-T is described in ClinVar as [Benign]. Clinvar id is 788273.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.23 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0136 (19827/1461530) while in subpopulation NFE AF= 0.0164 (18247/1111808). AF 95% confidence interval is 0.0162. There are 167 homozygotes in gnomad4_exome. There are 9519 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGH	NM_003878.3 linkuse as main transcript	c.174G>A	p.Ala58=	synonymous_variant	2/9	ENST00000260118.7	NP_003869.1
GGH	NM_001410926.1 linkuse as main transcript	c.174G>A	p.Ala58=	synonymous_variant	2/8		NP_001397855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGH	ENST00000260118.7 linkuse as main transcript	c.174G>A	p.Ala58=	synonymous_variant	2/9	1	NM_003878.3	ENSP00000260118	P1

Frequencies

GnomAD3 genomes

AF:

0.00857

AC:

1298

AN:

151468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00284

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00355

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00746

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.0147

Gnomad OTH

AF:

0.00529

GnomAD3 exomes

AF:

0.00776

AC:

1950

AN:

251214

Hom.:

AF XY:

0.00785

AC XY:

1066

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00308

Gnomad FIN exome

AF:

0.00711

Gnomad NFE exome

AF:

0.0133

Gnomad OTH exome

AF:

0.00718

GnomAD4 exome

AF:

0.0136

AC:

19827

AN:

1461530

Hom.:

167

Cov.:

AF XY:

0.0131

AC XY:

9519

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.00263

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.00306

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00333

Gnomad4 FIN exome

AF:

0.00719

Gnomad4 NFE exome

AF:

0.0164

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00857

AC:

1298

AN:

151538

Hom.:

Cov.:

AF XY:

0.00784

AC XY:

580

AN XY:

73962

show subpopulations

Gnomad4 AFR

AF:

0.00286

Gnomad4 AMR

AF:

0.00354

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00333

Gnomad4 FIN

AF:

0.00746

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.00526

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.00814

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.61

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over