chr11-211482-C-T

Variant names:

• chr11-211482-C-T
• rs2293168
• NM_001286134.2:c.969+133C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286134.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIC8A	NM_001286134.2	MANE Select	c.969+133C>T		intron	N/A	NP_001273063.1	Q9NPQ8-1
	RIC8A	NM_021932.6		c.969+133C>T		intron	N/A	NP_068751.4
	RIC8A	NM_001386941.1		c.981+133C>T		intron	N/A	NP_001373870.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIC8A	ENST00000526104.6	TSL:1 MANE Select	c.969+133C>T		intron	N/A	ENSP00000432008.1	Q9NPQ8-1
	RIC8A	ENST00000325207.9	TSL:1	c.969+133C>T		intron	N/A	ENSP00000325941.5	Q9NPQ8-3
	RIC8A	ENST00000527696.5	TSL:1	c.951+133C>T		intron	N/A	ENSP00000434833.1	Q9NPQ8-2

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

African (AFR) AF: 0.0900 AC: 1770 AN: 19668

American (AMR) AF: 0.210 AC: 3686 AN: 17562

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 507 AN: 15638

East Asian (EAS) AF: 0.404 AC: 12896 AN: 31888

South Asian (SAS) AF: 0.0739 AC: 3806 AN: 51472

European-Finnish (FIN) AF: 0.0212 AC: 663 AN: 31302

Middle Eastern (MID) AF: 0.0563 AC: 153 AN: 2718

European-Non Finnish (NFE) AF: 0.0332 AC: 21005 AN: 632470

Other (OTH) AF: 0.0735 AC: 2827 AN: 38452

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

African (AFR) AF: 0.0962 AC: 3987 AN: 41448

American (AMR) AF: 0.173 AC: 2636 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3464

East Asian (EAS) AF: 0.421 AC: 2163 AN: 5136

South Asian (SAS) AF: 0.0792 AC: 379 AN: 4784

European-Finnish (FIN) AF: 0.0194 AC: 206 AN: 10616

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2169 AN: 67978

Other (OTH) AF: 0.0802 AC: 169 AN: 2108

Alfa AF: 0.0513 Hom.: 1305

Bravo AF: 0.0953

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2293168; hg19: chr11-211482;