rs8179186

Variant names:

• chr15-26772389-G-A
• rs8179186
• NM_000814.6:c.240+13C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-26772389-G-A
• chr15-26772389-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000814.6(GABRB3):​c.240+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,603,122 control chromosomes in the GnomAD database, including 22,136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2039 hom., cov: 34)
  • Exomes 𝑓: 0.15 (20097 hom.)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.680
• Publications: 12 publications found

Genes affected

GABRB3 (HGNC:4083): (gamma-aminobutyric acid type A receptor subunit beta3) This gene encodes a member of the ligand-gated ionic channel family. The encoded protein is one the subunits of a multi-subunit chloride channel that serves as the receptor for gamma-aminobutyric acid, a major inhibitory neurotransmitter of the mammalian nervous system. This gene is located on the long arm of chromosome 15 in a cluster with two other genes encoding related subunits of the family. This gene may be associated with the pathogenesis of several disorders including Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]

GABRB3 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 43

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• epilepsy, childhood absence, susceptibility to, 5

  Inheritance: AD, Unknown Classification: DEFINITIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• childhood absence epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Lennox-Gastaut syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-26772389-G-A is Benign according to our data. Variant chr15-26772389-G-A is described in ClinVar as Benign. ClinVar VariationId is 256819.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000814.6. 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
	GABRB3	NM_000814.6	MANE Select	c.240+13C>T		intron	N/A	NP_000805.1	P28472-1
	GABRB3	NM_021912.5		c.240+13C>T		intron	N/A	NP_068712.1	X5DQY4
	GABRB3	NM_001278631.2		c.-112+13C>T		intron	N/A	NP_001265560.1	P28472-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB3	ENST00000311550.10	TSL:1 MANE Select	c.240+13C>T		intron	N/A	ENSP00000308725.5	P28472-1
	GABRB3	ENST00000541819.6	TSL:1	c.408+13C>T		intron	N/A	ENSP00000442408.2	F5H7N0
	GABRB3	ENST00000299267.9	TSL:1	c.240+13C>T		intron	N/A	ENSP00000299267.4	P28472-2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20639 AN: 152090 Hom.: 2033 Cov.: 34

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.191 AC: 44799 AN: 234610 AF XY: 0.185

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.388

Gnomad ASJ exome AF: 0.0998

Gnomad EAS exome AF: 0.314

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.154 AC: 223505 AN: 1450924 Hom.: 20097 Cov.: 31 AF XY: 0.155 AC XY: 111748 AN XY: 721278

African (AFR) AF: 0.0262 AC: 869 AN: 33206

American (AMR) AF: 0.377 AC: 16463 AN: 43646

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 2541 AN: 25868

East Asian (EAS) AF: 0.336 AC: 13142 AN: 39106

South Asian (SAS) AF: 0.204 AC: 17287 AN: 84826

European-Finnish (FIN) AF: 0.172 AC: 8937 AN: 52014

Middle Eastern (MID) AF: 0.0836 AC: 480 AN: 5744

European-Non Finnish (NFE) AF: 0.140 AC: 154918 AN: 1106638

Other (OTH) AF: 0.148 AC: 8868 AN: 59876

GnomAD4 genome AF: 0.136 AC: 20655 AN: 152198 Hom.: 2039 Cov.: 34 AF XY: 0.144 AC XY: 10690 AN XY: 74416

African (AFR) AF: 0.0349 AC: 1450 AN: 41570

American (AMR) AF: 0.289 AC: 4428 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1614 AN: 5122

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4826

European-Finnish (FIN) AF: 0.176 AC: 1870 AN: 10616

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.140 AC: 9495 AN: 67974

Other (OTH) AF: 0.136 AC: 288 AN: 2116

Alfa AF: 0.0830 Hom.: 149

Bravo AF: 0.139

Asia WGS AF: 0.256 AC: 889 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		0.68
PromoterAI		0.046	Neutral
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: rs8179186; hg19: chr15-27017536; COSMIC: COSV54689489; COSMIC: COSV54689489;