chr5-161689745-A-G

Variant names:

• chr5-161689745-A-G
• rs34826485
• NM_000811.3:c.639A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 1P and 11B. PP3 BP6_Moderate BP7 BS1 BS2

The NM_000811.3(GABRA6):​c.639A>G​(p.Gln213Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00766 in 1,613,366 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (146 hom.)
• Consequence: GABRA6 NM_000811.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.75
• Publications: 3 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 -10 ACMG points.

• PP3: REVEL computational evidence supports a deleterious effect, 0.672
• BP6: Variant 5-161689745-A-G is Benign according to our data. Variant chr5-161689745-A-G is described in ClinVar as Benign. ClinVar VariationId is 477867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.75 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00544 (829/152348) while in subpopulation SAS AF = 0.0381 (184/4830). AF 95% confidence interval is 0.0336. There are 9 homozygotes in GnomAd4. There are 408 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA6	NM_000811.3	MANE Select	c.639A>G	p.Gln213Gln	synonymous	Exon 6 of 9	NP_000802.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA6	ENST00000274545.10	TSL:1 MANE Select	c.639A>G	p.Gln213Gln	synonymous	Exon 6 of 9	ENSP00000274545.5
	GABRA6	ENST00000523217.5	TSL:5	c.609A>G	p.Gln203Gln	synonymous	Exon 6 of 9	ENSP00000430527.1
	GABRA6	ENST00000520000.5	TSL:4	c.456A>G	p.Gln152Gln	synonymous	Exon 4 of 5	ENSP00000429943.1

Frequencies

GnomAD3 genomes AF: 0.00545 AC: 829 AN: 152230 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0377

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.00861

GnomAD2 exomes AF: 0.00934 AC: 2347 AN: 251216 AF XY: 0.0116

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00416

Gnomad ASJ exome AF: 0.0126

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.00635

Gnomad OTH exome AF: 0.00965

GnomAD4 exome AF: 0.00789 AC: 11524 AN: 1461018 Hom.: 146 Cov.: 31 AF XY: 0.00914 AC XY: 6644 AN XY: 726878

African (AFR) AF: 0.00117 AC: 39 AN: 33460

American (AMR) AF: 0.00467 AC: 209 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 347 AN: 26122

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39626

South Asian (SAS) AF: 0.0407 AC: 3509 AN: 86224

European-Finnish (FIN) AF: 0.00198 AC: 106 AN: 53410

Middle Eastern (MID) AF: 0.0212 AC: 122 AN: 5758

European-Non Finnish (NFE) AF: 0.00600 AC: 6665 AN: 1111338

Other (OTH) AF: 0.00871 AC: 526 AN: 60358

GnomAD4 genome AF: 0.00544 AC: 829 AN: 152348 Hom.: 9 Cov.: 32 AF XY: 0.00548 AC XY: 408 AN XY: 74502

African (AFR) AF: 0.00103 AC: 43 AN: 41590

American (AMR) AF: 0.00431 AC: 66 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3464

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4830

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10626

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00657 AC: 447 AN: 68022

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00616 Hom.: 1

Bravo AF: 0.00471

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.00922

EpiControl AF: 0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Childhood absence epilepsy Benign:1

Jun 26, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.3
DANN	Benign	0.75
PhyloP100		2.7
Mutation Taster		=96/4	polymorphism

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: rs34826485; hg19: chr5-161116751;