chr5-162149139-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_198904.4(GABRG2):​c.954C>T​(p.Leu318Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

GABRG2
NM_198904.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0460

Publications

0 publications found
Variant links:
Genes affected
GABRG2 (HGNC:4087): (gamma-aminobutyric acid type A receptor subunit gamma2) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
GABRG2 Gene-Disease associations (from GenCC):
  • epilepsy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • developmental and epileptic encephalopathy, 74
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • febrile seizures, familial, 8
    Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
  • Dravet syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • generalized epilepsy with febrile seizures plus
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • self-limited epilepsy with centrotemporal spikes
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • undetermined early-onset epileptic encephalopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 5-162149139-C-T is Benign according to our data. Variant chr5-162149139-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 384407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.046 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00023 (35/152138) while in subpopulation AFR AF = 0.000845 (35/41432). AF 95% confidence interval is 0.000623. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GABRG2NM_198904.4 linkc.954C>T p.Leu318Leu synonymous_variant Exon 8 of 10 ENST00000639213.2 NP_944494.1 P18507-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GABRG2ENST00000639213.2 linkc.954C>T p.Leu318Leu synonymous_variant Exon 8 of 10 1 NM_198904.4 ENSP00000491909.2 P18507-2

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000845
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000478
AC:
12
AN:
251164
AF XY:
0.0000147
show subpopulations
Gnomad AFR exome
AF:
0.000677
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461744
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
727178
show subpopulations
African (AFR)
AF:
0.000866
AC:
29
AN:
33470
American (AMR)
AF:
0.0000224
AC:
1
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111914
Other (OTH)
AF:
0.0000662
AC:
4
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
4
7
11
14
18
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000230
AC:
35
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.000256
AC XY:
19
AN XY:
74300
show subpopulations
African (AFR)
AF:
0.000845
AC:
35
AN:
41432
American (AMR)
AF:
0.00
AC:
0
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5174
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68030
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000197
Hom.:
0
Bravo
AF:
0.000246

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Aug 31, 2017
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2;C1969810:Febrile seizures, familial, 8 Benign:1
Feb 02, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Inborn genetic diseases Benign:1
Jun 21, 2017
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
8.3
DANN
Benign
0.76
PhyloP100
-0.046

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

Other links and lift over

dbSNP: rs749531013; hg19: chr5-161576145; API