5-161697458-T-C

Variant names:

• chr5-161697458-T-C
• rs13172914
• NM_000811.3:c.1087-4040T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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.

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.1087-4040T>C		intron	N/A	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.1087-4040T>C		intron	N/A	ENSP00000274545.5	Q16445
	GABRA6	ENST00000523217.5	TSL:5	c.1057-4040T>C		intron	N/A	ENSP00000430527.1	E7EV53
	GABRA6	ENST00000521520.1	TSL:2	n.1080-4040T>C		intron	N/A

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

African (AFR) AF: 0.360 AC: 14926 AN: 41484

American (AMR) AF: 0.428 AC: 6536 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1823 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1570 AN: 5166

South Asian (SAS) AF: 0.429 AC: 2070 AN: 4824

European-Finnish (FIN) AF: 0.557 AC: 5887 AN: 10562

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38595 AN: 67966

Other (OTH) AF: 0.452 AC: 952 AN: 2106

Alfa AF: 0.534 Hom.: 4644

Bravo AF: 0.461

Asia WGS AF: 0.342 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.2
DANN	Benign	0.77
PhyloP100		0.10
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: rs13172914; hg19: chr5-161124464; COSMIC: COSV50878788;