Variant chr5-162067984-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_198904.4(GABRG2):c.-4dupA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 1,139,362 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 0.0019 ( 1 hom., cov: 31)

Exomes 𝑓: 0.052 ( 0 hom. )

Consequence

GABRG2
NM_198904.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: -0.142

Variant links:

Genes affected

GABRG2 (HGNC:4087): (gamma-aminobutyric acid type A receptor subunit gamma2) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GABRG2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 5-162067984-G-GA is Benign according to our data. Variant chr5-162067984-G-GA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 352636.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG2	NM_198904.4 link	c.-4dupA		5_prime_UTR_variant	Exon 1 of 10	ENST00000639213.2	NP_944494.1	P18507-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG2	ENST00000639213 link	c.-4dupA		5_prime_UTR_variant	Exon 1 of 10	1	NM_198904.4	ENSP00000491909.2		P18507-2

Frequencies

GnomAD3 genomes

AF:

0.00192

AC:

267

AN:

139270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00415

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00130

Gnomad ASJ

AF:

0.00364

Gnomad EAS

AF:

0.000624

Gnomad SAS

AF:

0.00390

Gnomad FIN

AF:

0.00109

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000740

Gnomad OTH

AF:

0.00157

GnomAD4 exome

AF:

0.0519

AC:

51900

AN:

1000048

Hom.:

Cov.:

AF XY:

0.0494

AC XY:

24800

AN XY:

502104

show subpopulations

Gnomad4 AFR exome

AF:

0.0495

Gnomad4 AMR exome

AF:

0.0258

Gnomad4 ASJ exome

AF:

0.0370

Gnomad4 EAS exome

AF:

0.0291

Gnomad4 SAS exome

AF:

0.0283

Gnomad4 FIN exome

AF:

0.0269

Gnomad4 NFE exome

AF:

0.0580

Gnomad4 OTH exome

AF:

0.0472

GnomAD4 genome

AF:

0.00193

AC:

269

AN:

139314

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

129

AN XY:

67450

show subpopulations

Gnomad4 AFR

AF:

0.00417

Gnomad4 AMR

AF:

0.00129

Gnomad4 ASJ

AF:

0.00364

Gnomad4 EAS

AF:

0.000626

Gnomad4 SAS

AF:

0.00392

Gnomad4 FIN

AF:

0.00109

Gnomad4 NFE

AF:

0.000740

Gnomad4 OTH

AF:

0.00207

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Generalized epilepsy with febrile seizures plus

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Severe myoclonic epilepsy in infancy

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jul 19, 2017

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over