5-161689700-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_000811.3(GABRA6):c.594C>A(p.Val198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,611,066 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (7 hom.)
• Consequence: GABRA6 NM_000811.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.359

Genes affected

GABRA6 (HGNC:4080): (gamma-aminobutyric acid type A receptor subunit alpha6) 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. At least 16 distinct subunits of GABA-A receptors have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 5-161689700-C-A is Benign according to our data. Variant chr5-161689700-C-A is described in ClinVar as [Benign]. Clinvar id is 767175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0053 (807/152238) while in subpopulation AFR AF= 0.0174 (723/41546). AF 95% confidence interval is 0.0164. There are 7 homozygotes in gnomad4. There are 377 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA6	NM_000811.3	c.594C>A	p.Val198=	synonymous_variant	6/9	ENST00000274545.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA6	ENST00000274545.10	c.594C>A	p.Val198=	synonymous_variant	6/9	1	NM_000811.3	P1

Frequencies

GnomAD3 genomes AF: 0.00529 AC: 805 AN: 152118 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00155 AC: 390 AN: 251202 Hom.: 3 AF XY: 0.00102 AC XY: 138 AN XY: 135818

Gnomad AFR exome AF: 0.0190

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.000620 AC: 905 AN: 1458828 Hom.: 7 Cov.: 31 AF XY: 0.000543 AC XY: 394 AN XY: 725924

Gnomad4 AFR exome AF: 0.0163

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.00171

GnomAD4 genome AF: 0.00530 AC: 807 AN: 152238 Hom.: 7 Cov.: 32 AF XY: 0.00506 AC XY: 377 AN XY: 74452

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00275 Hom.: 1

Bravo AF: 0.00607

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Childhood absence epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 03, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	2.9
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs143830239; hg19: chr5-161116706;