5-161701908-C-T

Position:

• chr5-161701908-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000811.3(GABRA6):​c.*135C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 938,038 control chromosomes in the GnomAD database, including 134,921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19695 hom., cov: 32)
  • Exomes 𝑓: 0.53 (115226 hom.)
• Consequence: GABRA6 NM_000811.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.520

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-161701908-C-T is Benign according to our data. Variant chr5-161701908-C-T is described in ClinVar as [Benign]. Clinvar id is 1169913.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA6	NM_000811.3	c.*135C>T		3_prime_UTR_variant	9/9	ENST00000274545.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA6	ENST00000274545.10	c.*135C>T		3_prime_UTR_variant	9/9	1	NM_000811.3	P1
GABRA6	ENST00000523217.5	c.*135C>T		3_prime_UTR_variant	9/9	5
GABRA6	ENST00000521520.1	n.1490C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76609 AN: 151838 Hom.: 19691 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.534 AC: 420094 AN: 786082 Hom.: 115226 Cov.: 10 AF XY: 0.532 AC XY: 217033 AN XY: 407704

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.368

Gnomad4 ASJ exome AF: 0.536

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.546

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.504 AC: 76629 AN: 151956 Hom.: 19695 Cov.: 32 AF XY: 0.502 AC XY: 37248 AN XY: 74252

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.484

Alfa AF: 0.546 Hom.: 38884

Bravo AF: 0.490

Asia WGS AF: 0.345 AC: 1201 AN: 3478

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

Apr 05, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
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: rs3219151; hg19: chr5-161128914; COSMIC: COSV50878678;