5-161293870-G-A

Position:

• chr5-161293870-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001371727.1(GABRB2):​c.*211C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 545,512 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (47 hom., cov: 32)
  • Exomes 𝑓: 0.028 (197 hom.)
• Consequence: GABRB2 NM_001371727.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.430

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 5-161293870-G-A is Benign according to our data. Variant chr5-161293870-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1217644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0222 (3373/152242) while in subpopulation NFE AF= 0.0357 (2425/68002). AF 95% confidence interval is 0.0345. There are 47 homozygotes in gnomad4. There are 1557 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3373 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB2	NM_001371727.1	c.*211C>T		3_prime_UTR_variant	10/10	ENST00000393959.6
GABRB2	NM_000813.3	c.*211C>T		3_prime_UTR_variant	10/10
GABRB2	NM_021911.3	c.*211C>T		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB2	ENST00000393959.6	c.*211C>T		3_prime_UTR_variant	10/10	1	NM_001371727.1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3373 AN: 152124 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.00649

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.0280 AC: 10996 AN: 393270 Hom.: 197 Cov.: 3 AF XY: 0.0275 AC XY: 5633 AN XY: 204642

Gnomad4 AFR exome AF: 0.00706

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.0169

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00988

Gnomad4 FIN exome AF: 0.0223

Gnomad4 NFE exome AF: 0.0367

Gnomad4 OTH exome AF: 0.0295

GnomAD4 genome AF: 0.0222 AC: 3373 AN: 152242 Hom.: 47 Cov.: 32 AF XY: 0.0209 AC XY: 1557 AN XY: 74438

Gnomad4 AFR AF: 0.00647

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00974

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0357

Gnomad4 OTH AF: 0.0274

Alfa AF: 0.0206 Hom.: 13

Bravo AF: 0.0217

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.2
DANN	Benign	0.56

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: rs34906738; hg19: chr5-160720877;