5-161697458-T-C

Position:

• chr5-161697458-T-C

Variant summary

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

The NM_000811.3(GABRA6):​c.1087-4040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,036 control chromosomes in the GnomAD database, including 18,227 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 0.48 (18227 hom., cov: 32)
• Consequence: GABRA6 NM_000811.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA6	NM_000811.3	c.1087-4040T>C		intron_variant		ENST00000274545.10	NP_000802.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA6	ENST00000274545.10	c.1087-4040T>C		intron_variant		1	NM_000811.3	ENSP00000274545	P1
GABRA6	ENST00000523217.5	c.1057-4040T>C		intron_variant		5		ENSP00000430527
GABRA6	ENST00000521520.1	n.1080-4040T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72881 AN: 151918 Hom.: 18226 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.479 AC: 72890 AN: 152036 Hom.: 18227 Cov.: 32 AF XY: 0.477 AC XY: 35480 AN XY: 74316

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.452

Alfa AF: 0.537 Hom.: 4576

Bravo AF: 0.461

Asia WGS AF: 0.342 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.2
DANN	Benign	0.77

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: rs13172914; hg19: chr5-161124464; COSMIC: COSV50878788;