5-161895658-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001127644.2(GABRA1):c.857-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABRA1 NM_001127644.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003600
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.150

Genes affected

GABRA1 (HGNC:4075): (gamma-aminobutyric acid type A receptor subunit alpha1) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene cause juvenile myoclonic epilepsy and childhood absence epilepsy type 4. Multiple transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 5-161895658-C-T is Benign according to our data. Variant chr5-161895658-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 468881.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-161895658-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA1	NM_001127644.2	c.857-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000393943.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA1	ENST00000393943.10	c.857-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001127644.2	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 21 AN: 148610 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.0000247

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: 0.000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000164

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000131 AC: 189 AN: 1441862 Hom.: 0 Cov.: 35 AF XY: 0.000125 AC XY: 90 AN XY: 717316

Gnomad4 AFR exome AF: 0.000799

Gnomad4 AMR exome AF: 0.000213

Gnomad4 ASJ exome AF: 0.000350

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.0000236

Gnomad4 FIN exome AF: 0.000271

Gnomad4 NFE exome AF: 0.0000982

Gnomad4 OTH exome AF: 0.000269

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000141 AC: 21 AN: 148610 Hom.: 0 Cov.: 31 AF XY: 0.000180 AC XY: 13 AN XY: 72322

Gnomad4 AFR AF: 0.0000247

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000944

Gnomad4 NFE AF: 0.000164

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0124 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Idiopathic generalized epilepsy;C1970160:Epilepsy, childhood absence 4;C4013473:Epilepsy, idiopathic generalized, susceptibility to, 13 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 09, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	3.2
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00036
dbscSNV1_RF	Benign	0.022
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs752572964; hg19: chr5-161322664; COSMIC: COSV50109512; COSMIC: COSV50109512;