rs12520992

Positions:

• chr5-162142424-A-C
• chr5-162142424-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198904.4(GABRG2):​c.922+108A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,150,928 control chromosomes in the GnomAD database, including 9,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (810 hom., cov: 32)
  • Exomes 𝑓: 0.12 (8671 hom.)
• Consequence: GABRG2 NM_198904.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.550

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-162142424-A-C is Benign according to our data. Variant chr5-162142424-A-C is described in ClinVar as [Benign]. Clinvar id is 675186.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG2	NM_198904.4	c.922+108A>C		intron_variant		ENST00000639213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG2	ENST00000639213.2	c.922+108A>C		intron_variant		1	NM_198904.4	A1

Frequencies

GnomAD3 genomes AF: 0.0893 AC: 13590 AN: 152158 Hom.: 810 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0748

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.0910

GnomAD4 exome AF: 0.124 AC: 123528 AN: 998652 Hom.: 8671 Cov.: 13 AF XY: 0.122 AC XY: 63098 AN XY: 515372

Gnomad4 AFR exome AF: 0.0240

Gnomad4 AMR exome AF: 0.0551

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.00168

Gnomad4 SAS exome AF: 0.0773

Gnomad4 FIN exome AF: 0.0961

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.0893 AC: 13596 AN: 152276 Hom.: 810 Cov.: 32 AF XY: 0.0860 AC XY: 6407 AN XY: 74466

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.0799

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.0755

Gnomad4 FIN AF: 0.0929

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.0910

Alfa AF: 0.0335 Hom.: 45

Bravo AF: 0.0862

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.68

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: rs12520992; hg19: chr5-161569430;