rs11246002

Positions:

• chr11-211447-G-A
• chr11-211447-G-C

Variant summary

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

The NM_001286134.2(RIC8A):​c.969+98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 1,298,186 control chromosomes in the GnomAD database, including 1,917 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 0.049 (232 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1685 hom.)
• Consequence: RIC8A NM_001286134.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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]

RIC8A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIC8A	NM_001286134.2	c.969+98G>A		intron_variant		ENST00000526104.6	NP_001273063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIC8A	ENST00000526104.6	c.969+98G>A		intron_variant		1	NM_001286134.2	ENSP00000432008.1

Frequencies

GnomAD3 genomes AF: 0.0492 AC: 7479 AN: 151964 Hom.: 233 Cov.: 32

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0416

GnomAD4 exome AF: 0.0471 AC: 54004 AN: 1146104 Hom.: 1685 Cov.: 15 AF XY: 0.0484 AC XY: 27541 AN XY: 569106

Gnomad4 AFR exome AF: 0.0648

Gnomad4 AMR exome AF: 0.0338

Gnomad4 ASJ exome AF: 0.0212

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.0975

Gnomad4 FIN exome AF: 0.0218

Gnomad4 NFE exome AF: 0.0417

Gnomad4 OTH exome AF: 0.0497

GnomAD4 genome AF: 0.0492 AC: 7475 AN: 152082 Hom.: 232 Cov.: 32 AF XY: 0.0496 AC XY: 3684 AN XY: 74346

Gnomad4 AFR AF: 0.0614

Gnomad4 AMR AF: 0.0458

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0987

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0415 Hom.: 21

Bravo AF: 0.0513

Asia WGS AF: 0.117 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.4
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs11246002; hg19: chr11-211447; COSMIC: COSV57315758; COSMIC: COSV57315758;