rs592403

chr5-161292977-A-Cchr5-161292977-A-T

Variant summary

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

The NM_001371727.1(GABRB2):c.*1104T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,008 control chromosomes in the GnomAD database, including 18,505 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 0.46 (18505 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GABRB2 NM_001371727.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

Genes affected

GABRB2 (HGNC:4082): (gamma-aminobutyric acid type A receptor subunit beta2) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 2 subunit. It is mapped to chromosome 5q34 in a cluster comprised of genes encoding alpha 1 and gamma 2 subunits of the GABA A receptor. Alternative splicing of this gene generates 2 transcript variants, differing by a 114 bp insertion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB2	NM_001371727.1	c.*1104T>G		3_prime_UTR_variant	10/10	ENST00000393959.6
GABRB2	NM_000813.3	c.*1104T>G		3_prime_UTR_variant	10/10
GABRB2	NM_021911.3	c.*1104T>G		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB2	ENST00000393959.6	c.*1104T>G		3_prime_UTR_variant	10/10	1	NM_001371727.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70146 AN: 151892 Hom.: 18473 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.465

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.462 AC: 70227 AN: 152008 Hom.: 18505 Cov.: 32 AF XY: 0.460 AC XY: 34163 AN XY: 74308

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.463

Alfa AF: 0.359 Hom.: 20370

Bravo AF: 0.495

Asia WGS AF: 0.444 AC: 1543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.2
Dann	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs592403; hg19: chr5-160719984;