5-161415416-C-T

Position:

• chr5-161415416-C-T

Variant summary

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

The NM_001371727.1(GABRB2):​c.459-4359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,972 control chromosomes in the GnomAD database, including 34,005 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 0.66 (34005 hom., cov: 32)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB2	NM_001371727.1	c.459-4359G>A		intron_variant		ENST00000393959.6
GABRB2	NM_000813.3	c.459-4359G>A		intron_variant
GABRB2	NM_021911.3	c.459-4359G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB2	ENST00000393959.6	c.459-4359G>A		intron_variant		1	NM_001371727.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99979 AN: 151854 Hom.: 33988 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.658 AC: 100038 AN: 151972 Hom.: 34005 Cov.: 32 AF XY: 0.660 AC XY: 49004 AN XY: 74270

Gnomad4 AFR AF: 0.470

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.634

Alfa AF: 0.697 Hom.: 5528

Bravo AF: 0.648

Asia WGS AF: 0.738 AC: 2568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.67

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: rs2962425; hg19: chr5-160842422; COSMIC: COSV50905515;