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GeneBe

X-151955509-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004961.4(GABRE):c.996G>A(p.Pro332=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,210,278 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 2 hem., cov: 24)
Exomes 𝑓: 0.000025 ( 0 hom. 6 hem. )

Consequence

GABRE
NM_004961.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.03
Variant links:
Genes affected
GABRE (HGNC:4085): (gamma-aminobutyric acid type A receptor subunit epsilon) The product of this gene belongs to the ligand-gated ionic channel (TC 1.A.9) family. It encodes the gamma-aminobutyric acid (GABA) A receptor which is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes an epsilon subunit. It is mapped to chromosome Xq28 in a cluster comprised of genes encoding alpha 3, beta 4 and theta subunits of the same receptor. Alternatively spliced transcript variants have been identified, but only one is thought to encode a protein. [provided by RefSeq, Oct 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-151955509-C-T is Benign according to our data. Variant chrX-151955509-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 916144.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=-3.03 with no splicing effect.
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 Hemizygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GABRENM_004961.4 linkuse as main transcriptc.996G>A p.Pro332= synonymous_variant 8/9 ENST00000370328.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GABREENST00000370328.4 linkuse as main transcriptc.996G>A p.Pro332= synonymous_variant 8/91 NM_004961.4 P1P78334-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000801
AC:
9
AN:
112316
Hom.:
0
Cov.:
24
AF XY:
0.0000580
AC XY:
2
AN XY:
34500
show subpopulations
Gnomad AFR
AF:
0.0000972
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000188
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000561
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000375
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000600
AC:
11
AN:
183209
Hom.:
0
AF XY:
0.0000443
AC XY:
3
AN XY:
67673
show subpopulations
Gnomad AFR exome
AF:
0.0000760
Gnomad AMR exome
AF:
0.000146
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000722
Gnomad SAS exome
AF:
0.0000524
Gnomad FIN exome
AF:
0.0000627
Gnomad NFE exome
AF:
0.0000367
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000246
AC:
27
AN:
1097962
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
6
AN XY:
363320
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.000114
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000662
Gnomad4 SAS exome
AF:
0.0000369
Gnomad4 FIN exome
AF:
0.0000741
Gnomad4 NFE exome
AF:
0.0000154
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000801
AC:
9
AN:
112316
Hom.:
0
Cov.:
24
AF XY:
0.0000580
AC XY:
2
AN XY:
34500
show subpopulations
Gnomad4 AFR
AF:
0.0000972
Gnomad4 AMR
AF:
0.000188
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000561
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000375
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000642
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
Cadd
Benign
2.5
Dann
Benign
0.87
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs141917924; hg19: chrX-151123981; API