rs7391474

Variant names:

• chrX-152451236-T-G
• rs7391474
• NM_000808.4:c.-117A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

GABRA3 Gene-Disease associations (from GenCC):

• epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000808.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA3	NM_000808.4	MANE Select	c.-117A>C		5_prime_UTR	Exon 1 of 10	NP_000799.1	P34903

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA3	ENST00000370314.9	TSL:1 MANE Select	c.-117A>C		5_prime_UTR	Exon 1 of 10	ENSP00000359337.4	P34903
	GABRA3	ENST00000862742.1		c.-191A>C		5_prime_UTR	Exon 1 of 11	ENSP00000532801.1
	GABRA3	ENST00000862743.1		c.-188A>C		5_prime_UTR	Exon 1 of 11	ENSP00000532802.1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 79544 AN: 109076 Hom.: 21046 Cov.: 22

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.333 AC: 1 AN: 3

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 1 AN: 1

East Asian (EAS) AF: 0.800 AC: 4 AN: 5

South Asian (SAS) AF: 0.00 AC: 0 AN: 1

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.836 AC: 102 AN: 122

Other (OTH) AF: 0.400 AC: 2 AN: 5

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

African (AFR) AF: 0.554 AC: 16320 AN: 29470

American (AMR) AF: 0.762 AC: 7931 AN: 10409

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2108 AN: 2617

East Asian (EAS) AF: 0.534 AC: 1812 AN: 3395

South Asian (SAS) AF: 0.659 AC: 1641 AN: 2491

European-Finnish (FIN) AF: 0.810 AC: 4715 AN: 5824

Middle Eastern (MID) AF: 0.741 AC: 157 AN: 212

European-Non Finnish (NFE) AF: 0.822 AC: 43181 AN: 52548

Other (OTH) AF: 0.719 AC: 1067 AN: 1484

Alfa AF: 0.761 Hom.: 11689

Bravo AF: 0.711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.91
DANN	Benign	0.82
PhyloP100		-0.052
PromoterAI		0.068	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7391474; hg19: chrX-151619708;