5-161701908-C-T

Variant names:

• chr5-161701908-C-T
• rs3219151
• NM_000811.3:c.*135C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 49 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000811.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA6	NM_000811.3	MANE Select	c.*135C>T		3_prime_UTR	Exon 9 of 9	NP_000802.2	Q16445

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA6	ENST00000274545.10	TSL:1 MANE Select	c.*135C>T		3_prime_UTR	Exon 9 of 9	ENSP00000274545.5	Q16445
	GABRA6	ENST00000523217.5	TSL:5	c.*135C>T		3_prime_UTR	Exon 9 of 9	ENSP00000430527.1	E7EV53
	GABRA6	ENST00000521520.1	TSL:2	n.1490C>T		non_coding_transcript_exon	Exon 3 of 3

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

African (AFR) AF: 0.444 AC: 8623 AN: 19412

American (AMR) AF: 0.368 AC: 12690 AN: 34530

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 10681 AN: 19940

East Asian (EAS) AF: 0.312 AC: 10653 AN: 34120

South Asian (SAS) AF: 0.447 AC: 28514 AN: 63846

European-Finnish (FIN) AF: 0.546 AC: 20210 AN: 37046

Middle Eastern (MID) AF: 0.498 AC: 1576 AN: 3166

European-Non Finnish (NFE) AF: 0.573 AC: 307264 AN: 536192

Other (OTH) AF: 0.526 AC: 19883 AN: 37830

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

African (AFR) AF: 0.442 AC: 18313 AN: 41438

American (AMR) AF: 0.447 AC: 6818 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1830 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1578 AN: 5162

South Asian (SAS) AF: 0.430 AC: 2072 AN: 4816

European-Finnish (FIN) AF: 0.554 AC: 5837 AN: 10542

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38617 AN: 67946

Other (OTH) AF: 0.484 AC: 1022 AN: 2110

Alfa AF: 0.542 Hom.: 86587

Bravo AF: 0.490

Asia WGS AF: 0.345 AC: 1201 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Childhood absence epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.77
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3219151; hg19: chr5-161128914; COSMIC: COSV50878678;