rs2293168

Positions:

• chr11-211482-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286134.2(RIC8A):​c.969+133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 993,170 control chromosomes in the GnomAD database, including 5,032 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.078 (1042 hom., cov: 32)
  • Exomes 𝑓: 0.056 (3990 hom.)
• Consequence: RIC8A NM_001286134.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967

Genes affected

RIC8A (HGNC:29550): (RIC8 guanine nucleotide exchange factor A) Predicted to enable G-protein alpha-subunit binding activity; GTPase activator activity; and guanyl-nucleotide exchange factor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within several processes, including basement membrane organization; gastrulation; and visual learning. Predicted to be located in membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIC8A	NM_001286134.2	c.969+133C>T		intron_variant		ENST00000526104.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIC8A	ENST00000526104.6	c.969+133C>T		intron_variant		1	NM_001286134.2	P4

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11797 AN: 151882 Hom.: 1033 Cov.: 32

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0805

GnomAD4 exome AF: 0.0562 AC: 47313 AN: 841170 Hom.: 3990 Cov.: 11 AF XY: 0.0564 AC XY: 23813 AN XY: 422520

Gnomad4 AFR exome AF: 0.0900

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.0739

Gnomad4 FIN exome AF: 0.0212

Gnomad4 NFE exome AF: 0.0332

Gnomad4 OTH exome AF: 0.0735

GnomAD4 genome AF: 0.0778 AC: 11831 AN: 152000 Hom.: 1042 Cov.: 32 AF XY: 0.0806 AC XY: 5990 AN XY: 74308

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.0792

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0802

Alfa AF: 0.0411 Hom.: 265

Bravo AF: 0.0953

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2293168; hg19: chr11-211482;