5-162130947-A-C

Variant names:

• chr5-162130947-A-C
• rs17060106
• NM_198904.4:c.770-11217A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198904.4(GABRG2):​c.770-11217A>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 152,016 control chromosomes in the GnomAD database, including 1,136 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 0.12 (1136 hom., cov: 32)
• Consequence: GABRG2 NM_198904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 74

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• febrile seizures, familial, 8

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Dravet syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• generalized epilepsy with febrile seizures plus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• self-limited epilepsy with centrotemporal spikes

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG2	NM_198904.4	c.770-11217A>C		intron_variant	Intron 6 of 9	ENST00000639213.2	NP_944494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG2	ENST00000639213.2	c.770-11217A>C		intron_variant	Intron 6 of 9	1	NM_198904.4	ENSP00000491909.2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18086 AN: 151898 Hom.: 1131 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.0943

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00541

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.119 AC: 18115 AN: 152016 Hom.: 1136 Cov.: 32 AF XY: 0.115 AC XY: 8574 AN XY: 74304

African (AFR) AF: 0.112 AC: 4659 AN: 41514

American (AMR) AF: 0.0942 AC: 1434 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3464

East Asian (EAS) AF: 0.00542 AC: 28 AN: 5166

South Asian (SAS) AF: 0.130 AC: 627 AN: 4826

European-Finnish (FIN) AF: 0.0836 AC: 888 AN: 10616

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9371 AN: 67888

Other (OTH) AF: 0.113 AC: 239 AN: 2110

Alfa AF: 0.0937 Hom.: 275

Bravo AF: 0.118

Asia WGS AF: 0.0820 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.70
PhyloP100		-0.75
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs17060106; hg19: chr5-161557953;