rs4906901

Positions:

• chr15-26773893-C-A
• chr15-26773893-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000541819.6(GABRB3):​c.249-1121G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 612,620 control chromosomes in the GnomAD database, including 263,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60168 hom., cov: 24)
  • Exomes 𝑓: 0.94 (203596 hom.)
• Consequence: GABRB3 ENST00000541819.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.265

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-26773893-C-A is Benign according to our data. Variant chr15-26773893-C-A is described in ClinVar as [Benign]. Clinvar id is 1239580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.26773893C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB3	ENST00000541819.6	c.249-1121G>T		intron_variant		1		ENSP00000442408.2
GABRB3	ENST00000638099.1	c.-20+50G>T		intron_variant		5		ENSP00000490678.1
GABRB3	ENST00000557641.5	n.453-1121G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.894 AC: 133733 AN: 149520 Hom.: 60139 Cov.: 24

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.901

GnomAD4 exome AF: 0.937 AC: 433761 AN: 463014 Hom.: 203596 Cov.: 5 AF XY: 0.939 AC XY: 228493 AN XY: 243230

Gnomad4 AFR exome AF: 0.775

Gnomad4 AMR exome AF: 0.938

Gnomad4 ASJ exome AF: 0.946

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.980

Gnomad4 FIN exome AF: 0.945

Gnomad4 NFE exome AF: 0.929

Gnomad4 OTH exome AF: 0.930

GnomAD4 genome AF: 0.894 AC: 133805 AN: 149606 Hom.: 60168 Cov.: 24 AF XY: 0.898 AC XY: 65426 AN XY: 72880

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.931

Gnomad4 ASJ AF: 0.951

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.984

Gnomad4 FIN AF: 0.944

Gnomad4 NFE AF: 0.932

Gnomad4 OTH AF: 0.902

Alfa AF: 0.913 Hom.: 12894

Bravo AF: 0.885

Asia WGS AF: 0.976 AC: 3393 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4906901; hg19: chr15-27019040;