rs551896139

Variant names:

• chr15-26642413-GTA-G
• rs551896139
• NM_000814.6:c.241-20881_241-20880delTA

Your query was ambiguous. Multiple possible variants found:

• chr15-26642413-GTA-G
• chr15-26642413-GTA-GTATA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000814.6(GABRB3):​c.241-20881_241-20880delTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000391 in 1,023,898 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB3	NM_000814.6	c.241-20881_241-20880delTA		intron_variant	Intron 3 of 8	ENST00000311550.10	NP_000805.1
GABRB3	NM_021912.5	c.241-20881_241-20880delTA		intron_variant	Intron 3 of 8		NP_068712.1
GABRB3	NM_001191320.2	c.-15-20881_-15-20880delTA		intron_variant	Intron 1 of 6		NP_001178249.1
GABRB3	NM_001278631.2	c.-16+18_-16+19delTA		intron_variant	Intron 4 of 9		NP_001265560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000311550.10	c.241-20881_241-20880delTA		intron_variant	Intron 3 of 8	1	NM_000814.6	ENSP00000308725.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000391 AC: 4 AN: 1023898 Hom.: 0 AF XY: 0.00000395 AC XY: 2 AN XY: 506034

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21954

American (AMR) AF: 0.00 AC: 0 AN: 27080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14586

East Asian (EAS) AF: 0.00 AC: 0 AN: 12144

South Asian (SAS) AF: 0.00 AC: 0 AN: 72910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3936

European-Non Finnish (NFE) AF: 0.00000487 AC: 4 AN: 821284

Other (OTH) AF: 0.00 AC: 0 AN: 37700

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.16

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: rs551896139; hg19: chr15-26887560;