rs34826485

chr5-161689745-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_000811.3(GABRA6):c.639A>G(p.Gln213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00766 in 1,613,366 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (146 hom.)
• Consequence: GABRA6 NM_000811.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.75

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 5-161689745-A-G is Benign according to our data. Variant chr5-161689745-A-G is described in ClinVar as [Benign]. Clinvar id is 477867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.75 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00544 (829/152348) while in subpopulation SAS AF= 0.0381 (184/4830). AF 95% confidence interval is 0.0336. There are 9 homozygotes in gnomad4. There are 408 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA6	NM_000811.3	c.639A>G	p.Gln213=	synonymous_variant	6/9	ENST00000274545.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA6	ENST00000274545.10	c.639A>G	p.Gln213=	synonymous_variant	6/9	1	NM_000811.3	P1

Frequencies

GnomAD3 genomes AF: 0.00545 AC: 829 AN: 152230 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0377

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.00934 AC: 2347 AN: 251216 Hom.: 39 AF XY: 0.0116 AC XY: 1570 AN XY: 135826

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00416

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0406

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.00635

Gnomad OTH exome AF: 0.00965

GnomAD4 exome AF: 0.00789 AC: 11524 AN: 1461018 Hom.: 146 Cov.: 31 AF XY: 0.00914 AC XY: 6644 AN XY: 726878

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.00467

Gnomad4 ASJ exome AF: 0.0133

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0407

Gnomad4 FIN exome AF: 0.00198

Gnomad4 NFE exome AF: 0.00600

Gnomad4 OTH exome AF: 0.00871

GnomAD4 genome AF: 0.00544 AC: 829 AN: 152348 Hom.: 9 Cov.: 32 AF XY: 0.00548 AC XY: 408 AN XY: 74502

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0381

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00657

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00616 Hom.: 1

Bravo AF: 0.00471

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.00922

EpiControl AF: 0.0109

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

Jun 26, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	6.3
Dann	Benign	0.75

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: rs34826485; hg19: chr5-161116751;