dbSNP rs3811991: GABRA6:c.1087-95A>C (chr5-161701403-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000811.3(GABRA6):c.1087-95A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,345,212 control chromosomes in the GnomAD database, including 248,590 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 0.56 ( 24712 hom., cov: 33)

Exomes 𝑓: 0.61 ( 223878 hom. )

Consequence

GABRA6
NM_000811.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780

Publications

8 publications found

Variant links:

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]

GABRA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 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.1087-95A>C		intron	N/A	NP_000802.2	Q16445

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GABRA6	ENST00000274545.10	TSL:1 MANE Select	c.1087-95A>C	intron	N/A	ENSP00000274545.5	Q16445
GABRA6	ENST00000523217.5	TSL:5	c.1057-95A>C	intron	N/A	ENSP00000430527.1	E7EV53
GABRA6	ENST00000521520.1	TSL:2	n.1080-95A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.563

AC:

85547

AN:

151970

Hom.:

24710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.631

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.483

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.566

GnomAD4 exome

AF:

0.606

AC:

722780

AN:

1193124

Hom.:

223878

AF XY:

0.604

AC XY:

366914

AN XY:

607300

show subpopulations

African (AFR)

AF:

0.485

AC:

13699

AN:

28258

American (AMR)

AF:

0.407

AC:

17911

AN:

43996

Ashkenazi Jewish (ASJ)

AF:

0.628

AC:

15318

AN:

24404

East Asian (EAS)

AF:

0.311

AC:

11947

AN:

38452

South Asian (SAS)

AF:

0.500

AC:

40160

AN:

80358

European-Finnish (FIN)

AF:

0.600

AC:

25168

AN:

41978

Middle Eastern (MID)

AF:

0.603

AC:

2799

AN:

4638

European-Non Finnish (NFE)

AF:

0.643

AC:

565126

AN:

879160

Other (OTH)

AF:

0.591

AC:

30652

AN:

51880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14475

28950

43426

57901

72376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13196

26392

39588

52784

65980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.563

AC:

85568

AN:

152088

Hom.:

24712

Cov.:

AF XY:

0.558

AC XY:

41517

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.481

AC:

19930

AN:

41474

American (AMR)

AF:

0.507

AC:

7752

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.631

AC:

2190

AN:

3468

East Asian (EAS)

AF:

0.305

AC:

1578

AN:

5180

South Asian (SAS)

AF:

0.482

AC:

2322

AN:

4816

European-Finnish (FIN)

AF:

0.607

AC:

6421

AN:

10574

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.640

AC:

43538

AN:

67978

Other (OTH)

AF:

0.560

AC:

1185

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1901

3802

5702

7603

9504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.581

Hom.:

5106

Bravo

AF:

0.549

Asia WGS

AF:

0.377

AC:

1312

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.6

(source)

DANN

Benign

0.54

PhyloP100

-0.078

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over