chr5-162067984-GAA-G

Variant names:

• chr5-162067984-GAA-G
• rs771282908
• NM_198904.4:c.-5_-4delAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_198904.4(GABRG2):​c.-5_-4delAA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000382 in 1,253,680 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (0 hom.)
• Consequence: GABRG2 NM_198904.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.819

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000428 (477/1114258) while in subpopulation NFE AF= 0.000448 (371/828916). AF 95% confidence interval is 0.00041. There are 0 homozygotes in gnomad4_exome. There are 224 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 477 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000143 AC: 2 AN: 139378 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000719

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000121

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000428 AC: 477 AN: 1114258 Hom.: 0 AF XY: 0.000399 AC XY: 224 AN XY: 561226

Gnomad4 AFR exome AF: 0.000421

Gnomad4 AMR exome AF: 0.000131

Gnomad4 ASJ exome AF: 0.000281

Gnomad4 EAS exome AF: 0.000189

Gnomad4 SAS exome AF: 0.000253

Gnomad4 FIN exome AF: 0.000982

Gnomad4 NFE exome AF: 0.000448

Gnomad4 OTH exome AF: 0.000386

GnomAD4 genome AF: 0.0000143 AC: 2 AN: 139422 Hom.: 0 Cov.: 31 AF XY: 0.0000148 AC XY: 1 AN XY: 67526

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000121

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00124 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs771282908; hg19: chr5-161494990;