5-162071731-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198904.4(GABRG2):c.107+3625T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,650 control chromosomes in the GnomAD database, including 28,802 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (28802 hom., cov: 31)
• Consequence: GABRG2 NM_198904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG2	NM_198904.4	c.107+3625T>C		intron_variant		ENST00000639213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG2	ENST00000639213.2	c.107+3625T>C		intron_variant		1	NM_198904.4	A1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93219 AN: 151532 Hom.: 28765 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.586

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.615 AC: 93308 AN: 151650 Hom.: 28802 Cov.: 31 AF XY: 0.612 AC XY: 45364 AN XY: 74104

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.585

Alfa AF: 0.621 Hom.: 39853

Bravo AF: 0.613

Asia WGS AF: 0.682 AC: 2372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.77
Dann	Benign	0.35

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: rs183294; hg19: chr5-161498737;