chr5-161294090-A-G

Variant names:

• chr5-161294090-A-G
• rs200872771
• NM_001371727.1:c.1530T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001371727.1(GABRB2):​c.1530T>C​(p.Tyr510Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,610,300 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000053 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: GABRB2 NM_001371727.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.82
• Publications: 0 publications found

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]

GABRB2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 92

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 5-161294090-A-G is Benign according to our data. Variant chr5-161294090-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 533532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000525 (8/152326) while in subpopulation AMR AF = 0.000327 (5/15306). AF 95% confidence interval is 0.000129. There are 1 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.1530T>C	p.Tyr510Tyr	synonymous_variant	Exon 10 of 10	ENST00000393959.6	NP_001358656.1
GABRB2	NM_021911.3	c.1530T>C	p.Tyr510Tyr	synonymous_variant	Exon 11 of 11		NP_068711.1
GABRB2	NM_000813.3	c.1416T>C	p.Tyr472Tyr	synonymous_variant	Exon 10 of 10		NP_000804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.1530T>C	p.Tyr510Tyr	synonymous_variant	Exon 10 of 10	1	NM_001371727.1	ENSP00000377531.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152208 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000758 AC: 19 AN: 250752 AF XY: 0.0000664

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.0000206 AC: 30 AN: 1457974 Hom.: 0 Cov.: 30 AF XY: 0.0000207 AC XY: 15 AN XY: 724654

African (AFR) AF: 0.0000300 AC: 1 AN: 33330

American (AMR) AF: 0.000314 AC: 14 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5738

European-Non Finnish (NFE) AF: 0.00000631 AC: 7 AN: 1108872

Other (OTH) AF: 0.0000996 AC: 6 AN: 60230

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152326 Hom.: 1 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74480

African (AFR) AF: 0.0000481 AC: 2 AN: 41594

American (AMR) AF: 0.000327 AC: 5 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000718

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Apr 01, 2021

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Intellectual disability Benign:1

Oct 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.8
DANN	Benign	0.48
PhyloP100		1.8

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

Other links and lift over

dbSNP: rs200872771; hg19: chr5-160721097;