rs551896139

chr15-26642413-G-GTA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000814.6(GABRB3):c.241-20880_241-20879insTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,176,028 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (9 hom.)
• Consequence: GABRB3 NM_000814.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.318

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 15-26642413-G-GTA is Benign according to our data. Variant chr15-26642413-G-GTA is described in ClinVar as [Likely_benign]. Clinvar id is 445708.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 513 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB3	NM_000814.6	c.241-20880_241-20879insTA		intron_variant		ENST00000311550.10
GABRB3	NM_001191320.2	c.-15-20880_-15-20879insTA		intron_variant
GABRB3	NM_001278631.2	c.-16+19_-16+20insTA		intron_variant
GABRB3	NM_021912.5	c.241-20880_241-20879insTA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB3	ENST00000311550.10	c.241-20880_241-20879insTA		intron_variant		1	NM_000814.6	P1

Frequencies

GnomAD3 genomes AF: 0.00337 AC: 513 AN: 152060 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00992

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00522

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00355 AC: 3639 AN: 1023850 Hom.: 9 Cov.: 14 AF XY: 0.00343 AC XY: 1737 AN XY: 506018

Gnomad4 AFR exome AF: 0.000547

Gnomad4 AMR exome AF: 0.000923

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000411

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.00401

Gnomad4 OTH exome AF: 0.00318

GnomAD4 genome AF: 0.00337 AC: 513 AN: 152178 Hom.: 3 Cov.: 32 AF XY: 0.00336 AC XY: 250 AN XY: 74392

Gnomad4 AFR AF: 0.000723

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00992

Gnomad4 NFE AF: 0.00522

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00475 Hom.: 1

Bravo AF: 0.00228

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Sep 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs551896139; hg19: chr15-26887560;