chr5-161293870-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.430
Variant links:
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]

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ACMG classification

Classification made for transcript

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
GABRB2NM_001371727.1 linkuse as main transcriptc.*211C>T 3_prime_UTR_variant 10/10 ENST00000393959.6
GABRB2NM_000813.3 linkuse as main transcriptc.*211C>T 3_prime_UTR_variant 10/10
GABRB2NM_021911.3 linkuse as main transcriptc.*211C>T 3_prime_UTR_variant 11/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GABRB2ENST00000393959.6 linkuse as main transcriptc.*211C>T 3_prime_UTR_variant 10/101 NM_001371727.1 P47870-2

Frequencies

GnomAD3 genomes
AF:
0.0222
AC:
3373
AN:
152124
Hom.:
47
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxJul 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34906738; hg19: chr5-160720877; API