rs11959228

Positions:

• chr5-161700105-A-G
• chr5-161700105-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000274545.10(GABRA6):​c.1087-1393A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,170 control chromosomes in the GnomAD database, including 47,205 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (47205 hom., cov: 33)
• Consequence: GABRA6 ENST00000274545.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA6	NM_000811.3	c.1087-1393A>G		intron_variant		ENST00000274545.10	NP_000802.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA6	ENST00000274545.10	c.1087-1393A>G		intron_variant		1	NM_000811.3	ENSP00000274545	P1
GABRA6	ENST00000523217.5	c.1057-1393A>G		intron_variant		5		ENSP00000430527
GABRA6	ENST00000521520.1	n.1080-1393A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119326 AN: 152052 Hom.: 47190 Cov.: 33

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.785

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.785 AC: 119395 AN: 152170 Hom.: 47205 Cov.: 33 AF XY: 0.782 AC XY: 58168 AN XY: 74422

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.833

Gnomad4 OTH AF: 0.785

Alfa AF: 0.807 Hom.: 6312

Bravo AF: 0.772

Asia WGS AF: 0.772 AC: 2684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.58

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: rs11959228; hg19: chr5-161127111; COSMIC: COSV50878807;