5-161847217-GA-G

Position:

• chr5-161847217-GA-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The ENST00000023897.10(GABRA1):​c.-438del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000696 in 152,276 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00070 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABRA1 ENST00000023897.10 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.768

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]

LOC105377696 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 5-161847217-GA-G is Benign according to our data. Variant chr5-161847217-GA-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 352584.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000696 (106/152276) while in subpopulation SAS AF= 0.0145 (70/4826). AF 95% confidence interval is 0.0118. There are 1 homozygotes in gnomad4. There are 78 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105377696	XR_941158.4	n.74+3302del		intron_variant, non_coding_transcript_variant
GABRA1	NM_000806.5	c.-438del		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA1	ENST00000023897.10	c.-438del		5_prime_UTR_variant	1/11	1		P1
GABRA1	ENST00000638112.1	c.-493del		5_prime_UTR_variant	1/11	5		P1

Frequencies

GnomAD3 genomes AF: 0.000690 AC: 105 AN: 152158 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.000696 AC: 106 AN: 152276 Hom.: 1 Cov.: 30 AF XY: 0.00105 AC XY: 78 AN XY: 74450

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.000314

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Juvenile myoclonic epilepsy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

GABRA1: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

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: rs112361424; hg19: chr5-161274223;