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X-151955538-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004961.4(GABRE):c.967T>C(p.Leu323=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,210,473 control chromosomes in the GnomAD database, including 22 homozygotes. There are 665 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 9 hom., 342 hem., cov: 24)
Exomes 𝑓: 0.0011 ( 13 hom. 323 hem. )

Consequence

GABRE
NM_004961.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.467
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 -15 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=-0.86).
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-151955538-A-G is Benign according to our data. Variant chrX-151955538-A-G is described in ClinVar as [Benign]. Clinvar id is 717764.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=-0.467 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0109 (1231/112549) while in subpopulation AFR AF= 0.0364 (1127/30966). AF 95% confidence interval is 0.0346. There are 9 homozygotes in gnomad4. There are 342 alleles in male gnomad4 subpopulation. Median coverage is 24. 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 9 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GABRENM_004961.4 linkuse as main transcriptc.967T>C p.Leu323= synonymous_variant 8/9 ENST00000370328.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GABREENST00000370328.4 linkuse as main transcriptc.967T>C p.Leu323= synonymous_variant 8/91 NM_004961.4 P1P78334-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0110
AC:
1232
AN:
112495
Hom.:
9
Cov.:
24
AF XY:
0.00990
AC XY:
343
AN XY:
34649
show subpopulations
Gnomad AFR
AF:
0.0365
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00719
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00417
Gnomad NFE
AF:
0.000131
Gnomad OTH
AF:
0.0125
GnomAD3 exomes
AF:
0.00295
AC:
541
AN:
183271
Hom.:
9
AF XY:
0.00202
AC XY:
137
AN XY:
67711
show subpopulations
Gnomad AFR exome
AF:
0.0344
Gnomad AMR exome
AF:
0.00273
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000105
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000611
Gnomad OTH exome
AF:
0.00132
GnomAD4 exome
AF:
0.00110
AC:
1203
AN:
1097924
Hom.:
13
Cov.:
31
AF XY:
0.000889
AC XY:
323
AN XY:
363278
show subpopulations
Gnomad4 AFR exome
AF:
0.0341
Gnomad4 AMR exome
AF:
0.00290
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000924
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000796
Gnomad4 OTH exome
AF:
0.00219
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0109
AC:
1231
AN:
112549
Hom.:
9
Cov.:
24
AF XY:
0.00985
AC XY:
342
AN XY:
34713
show subpopulations
Gnomad4 AFR
AF:
0.0364
Gnomad4 AMR
AF:
0.00718
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000131
Gnomad4 OTH
AF:
0.0124
Alfa
AF:
0.00638
Hom.:
38
Bravo
AF:
0.0121
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 testingInvitaeSep 29, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
Cadd
Benign
1.5
Dann
Benign
0.42
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs112646382; hg19: chrX-151124010; API