11-214421-G-C

Variant names:

• chr11-214421-G-C
• rs3216
• NM_001286134.2:c.*71G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286134.2(RIC8A):​c.*71G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,542,762 control chromosomes in the GnomAD database, including 31,115 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 0.17 (2479 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28636 hom.)
• Consequence: RIC8A NM_001286134.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 16 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIC8A	NM_001286134.2	c.*71G>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000526104.6	NP_001273063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIC8A	ENST00000526104.6	c.*71G>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_001286134.2	ENSP00000432008.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25714 AN: 151914 Hom.: 2478 Cov.: 32

Gnomad AFR AF: 0.0841

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.191

GnomAD2 exomes AF: 0.175 AC: 27065 AN: 154812 AF XY: 0.178

Gnomad AFR exome AF: 0.0759

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.0971

Gnomad FIN exome AF: 0.223

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.200 AC: 277749 AN: 1390730 Hom.: 28636 Cov.: 28 AF XY: 0.199 AC XY: 136868 AN XY: 686604

African (AFR) AF: 0.0822 AC: 2588 AN: 31498

American (AMR) AF: 0.120 AC: 4278 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6508 AN: 25146

East Asian (EAS) AF: 0.136 AC: 4865 AN: 35726

South Asian (SAS) AF: 0.148 AC: 11677 AN: 79116

European-Finnish (FIN) AF: 0.213 AC: 10060 AN: 47170

Middle Eastern (MID) AF: 0.227 AC: 1291 AN: 5686

European-Non Finnish (NFE) AF: 0.210 AC: 225224 AN: 1072928

Other (OTH) AF: 0.195 AC: 11258 AN: 57760

GnomAD4 genome AF: 0.169 AC: 25715 AN: 152032 Hom.: 2479 Cov.: 32 AF XY: 0.169 AC XY: 12570 AN XY: 74300

African (AFR) AF: 0.0844 AC: 3499 AN: 41470

American (AMR) AF: 0.158 AC: 2414 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3468

East Asian (EAS) AF: 0.112 AC: 578 AN: 5162

South Asian (SAS) AF: 0.153 AC: 739 AN: 4818

European-Finnish (FIN) AF: 0.223 AC: 2358 AN: 10580

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14446 AN: 67952

Other (OTH) AF: 0.189 AC: 398 AN: 2106

Alfa AF: 0.150 Hom.: 458

Bravo AF: 0.161

Asia WGS AF: 0.129 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.095
DANN	Benign	0.61
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3216; hg19: chr11-214421; COSMIC: COSV57342826; COSMIC: COSV57342826;