rs7735530

Variant names:

• chr5-161869224-G-A
• rs7735530
• NM_001127644.2:c.255+3436G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-161869224-G-A
• chr5-161869224-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127644.2(GABRA1):​c.255+3436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,068 control chromosomes in the GnomAD database, including 3,222 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 0.18 (3222 hom., cov: 32)
• Consequence: GABRA1 NM_001127644.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331

Genes affected

GABRA1 (HGNC:4075): (gamma-aminobutyric acid type A receptor subunit alpha1) This gene encodes a gamma-aminobutyric acid (GABA) receptor. 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. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene cause juvenile myoclonic epilepsy and childhood absence epilepsy type 4. Multiple transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA1	NM_001127644.2	c.255+3436G>A		intron_variant	Intron 4 of 9	ENST00000393943.10	NP_001121116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA1	ENST00000393943.10	c.255+3436G>A		intron_variant	Intron 4 of 9	1	NM_001127644.2	ENSP00000377517.4

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27137 AN: 151952 Hom.: 3221 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27144 AN: 152068 Hom.: 3222 Cov.: 32 AF XY: 0.178 AC XY: 13257 AN XY: 74312

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.151

Alfa AF: 0.155 Hom.: 364

Bravo AF: 0.184

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.2
DANN	Benign	0.35

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: rs7735530; hg19: chr5-161296230;