rs2229944

Variant names:

• chr5-161294312-G-A
• rs2229944
• NM_001371727.1:c.1308C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-161294312-G-A
• chr5-161294312-G-C
• chr5-161294312-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001371727.1(GABRB2):​c.1308C>T​(p.Ala436Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,614,038 control chromosomes in the GnomAD database, including 7,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1112 hom., cov: 32)
  • Exomes 𝑓: 0.083 (6622 hom.)
• Consequence: GABRB2 NM_001371727.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.17
• Publications: 19 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):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy 92

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), 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=-0.51).
• BP6: Variant 5-161294312-G-A is Benign according to our data. Variant chr5-161294312-G-A is described in ClinVar as Benign. ClinVar VariationId is 380805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371727.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	NM_001371727.1	MANE Select	c.1308C>T	p.Ala436Ala	synonymous	Exon 10 of 10	NP_001358656.1	P47870-2
	GABRB2	NM_021911.3		c.1308C>T	p.Ala436Ala	synonymous	Exon 11 of 11	NP_068711.1	P47870-2
	GABRB2	NM_000813.3		c.1194C>T	p.Ala398Ala	synonymous	Exon 10 of 10	NP_000804.1	P47870-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	ENST00000393959.6	TSL:1 MANE Select	c.1308C>T	p.Ala436Ala	synonymous	Exon 10 of 10	ENSP00000377531.1	P47870-2
	GABRB2	ENST00000353437.10	TSL:1	c.1194C>T	p.Ala398Ala	synonymous	Exon 10 of 10	ENSP00000274546.6	P47870-1
	GABRB2	ENST00000520240.5	TSL:1	c.1194C>T	p.Ala398Ala	synonymous	Exon 10 of 10	ENSP00000429320.1	P47870-1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16818 AN: 152092 Hom.: 1109 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.0837

Gnomad EAS AF: 0.0378

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.131

GnomAD2 exomes AF: 0.114 AC: 28696 AN: 251182 AF XY: 0.107

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.0889

Gnomad EAS exome AF: 0.0387

Gnomad FIN exome AF: 0.0917

Gnomad NFE exome AF: 0.0769

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.0834 AC: 121979 AN: 1461828 Hom.: 6622 Cov.: 31 AF XY: 0.0834 AC XY: 60629 AN XY: 727216

African (AFR) AF: 0.153 AC: 5123 AN: 33474

American (AMR) AF: 0.282 AC: 12615 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0881 AC: 2303 AN: 26136

East Asian (EAS) AF: 0.0298 AC: 1185 AN: 39700

South Asian (SAS) AF: 0.111 AC: 9570 AN: 86254

European-Finnish (FIN) AF: 0.0913 AC: 4877 AN: 53420

Middle Eastern (MID) AF: 0.168 AC: 969 AN: 5768

European-Non Finnish (NFE) AF: 0.0715 AC: 79546 AN: 1111970

Other (OTH) AF: 0.0959 AC: 5791 AN: 60392

GnomAD4 genome AF: 0.111 AC: 16839 AN: 152210 Hom.: 1112 Cov.: 32 AF XY: 0.112 AC XY: 8355 AN XY: 74420

African (AFR) AF: 0.147 AC: 6117 AN: 41532

American (AMR) AF: 0.211 AC: 3224 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0837 AC: 290 AN: 3466

East Asian (EAS) AF: 0.0379 AC: 196 AN: 5174

South Asian (SAS) AF: 0.117 AC: 566 AN: 4820

European-Finnish (FIN) AF: 0.0861 AC: 913 AN: 10606

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0757 AC: 5150 AN: 68006

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.0921 Hom.: 2256

Bravo AF: 0.122

Asia WGS AF: 0.102 AC: 355 AN: 3478

EpiCase AF: 0.0843

EpiControl AF: 0.0817

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.7
DANN	Benign	0.70
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs2229944; hg19: chr5-160721319; COSMIC: COSV50955269;