rs7391474

Positions:

• chrX-152451236-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000808.4(GABRA3):​c.-117A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (21039 hom., 23265 hem., cov: 22)
  • Exomes 𝑓: 0.80 (18 hom. 67 hem.)
  • Failed GnomAD Quality Control
• Consequence: GABRA3 NM_000808.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0520

Genes affected

GABRA3 (HGNC:4077): (gamma-aminobutyric acid type A receptor subunit alpha3) 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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant X-152451236-T-G is Benign according to our data. Variant chrX-152451236-T-G is described in ClinVar as [Benign]. Clinvar id is 1241796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA3	NM_000808.4	c.-117A>C		5_prime_UTR_variant	1/10	ENST00000370314.9	NP_000799.1
GABRA3	XM_006724811.4	c.-117A>C		5_prime_UTR_variant	1/9		XP_006724874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA3	ENST00000370314.9	c.-117A>C		5_prime_UTR_variant	1/10	1	NM_000808.4	ENSP00000359337	P1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 79544 AN: 109076 Hom.: 21046 Cov.: 22 AF XY: 0.728 AC XY: 23247 AN XY: 31936

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.729

GnomAD4 exome AF: 0.804 AC: 115 AN: 143 Hom.: 18 Cov.: 0 AF XY: 0.848 AC XY: 67 AN XY: 79

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.800

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.729 AC: 79544 AN: 109125 Hom.: 21039 Cov.: 22 AF XY: 0.727 AC XY: 23265 AN XY: 31997

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.822

Gnomad4 OTH AF: 0.719

Alfa AF: 0.761 Hom.: 11689

Bravo AF: 0.711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.91
DANN	Benign	0.82

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: rs7391474; hg19: chrX-151619708;