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GeneBe

rs11786893

chr8-63035706-C-T

Variant summary

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

The NM_003878.3(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
NM_003878.3 synonymous

Scores

2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.23 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GGHNM_003878.3 linkuse as main transcriptc.174G>A p.Ala58= synonymous_variant 2/9 ENST00000260118.7
GGHNM_001410926.1 linkuse as main transcriptc.174G>A p.Ala58= synonymous_variant 2/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GGHENST00000260118.7 linkuse as main transcriptc.174G>A p.Ala58= synonymous_variant 2/91 NM_003878.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00857
AC:
1298
AN:
151468
Hom.:
5
Cov.:
32
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.:
15
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.:
34
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00857
AC:
1298
AN:
151538
Hom.:
5
Cov.:
32
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.:
14
Bravo
AF:
0.00814
Asia WGS
AF:
0.00144
AC:
5
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 submitterclinical testingInvitaeJun 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.26
Cadd
Benign
13
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.

Other links and lift over

dbSNP: rs11786893; hg19: chr8-63948265; COSMIC: COSV52650842; API