rs28551016

Positions:

• chr15-26940159-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000810.4(GABRA5):​c.877+82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 1,253,772 control chromosomes in the GnomAD database, including 77 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 0.014 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (37 hom.)
• Consequence: GABRA5 NM_000810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

Genes affected

GABRA5 (HGNC:4079): (gamma-aminobutyric acid type A receptor subunit alpha5) 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. Transcript variants utilizing three different alternative non-coding first exons have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2172/152236) while in subpopulation AFR AF= 0.0459 (1905/41536). AF 95% confidence interval is 0.0441. There are 40 homozygotes in gnomad4. There are 1013 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2172 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA5	NM_000810.4	c.877+82C>T		intron_variant		ENST00000335625.10	NP_000801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA5	ENST00000335625.10	c.877+82C>T		intron_variant		1	NM_000810.4	ENSP00000335592	P1
GABRA5	ENST00000355395.9	c.877+82C>T		intron_variant		5		ENSP00000347557	P1
GABRA5	ENST00000400081.7	c.877+82C>T		intron_variant		5		ENSP00000382953	P1

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2167 AN: 152116 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00924

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00237 AC: 2608 AN: 1101536 Hom.: 37 AF XY: 0.00223 AC XY: 1219 AN XY: 547846

Gnomad4 AFR exome AF: 0.0458

Gnomad4 AMR exome AF: 0.00709

Gnomad4 ASJ exome AF: 0.00601

Gnomad4 EAS exome AF: 0.0000294

Gnomad4 SAS exome AF: 0.000800

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000789

Gnomad4 OTH exome AF: 0.00663

GnomAD4 genome AF: 0.0143 AC: 2172 AN: 152236 Hom.: 40 Cov.: 32 AF XY: 0.0136 AC XY: 1013 AN XY: 74442

Gnomad4 AFR AF: 0.0459

Gnomad4 AMR AF: 0.00922

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000838

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.00427 Hom.: 11

Bravo AF: 0.0166

Asia WGS AF: 0.00606 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.81
DANN	Benign	0.66

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: rs28551016; hg19: chr15-27185306;