chr11-214544-C-T

Variant names:

• chr11-214544-C-T
• rs10081
• NM_001286134.2:c.*194C>T

Variant summary

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

The NM_001286134.2(RIC8A):​c.*194C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 712,940 control chromosomes in the GnomAD database, including 10,468 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 0.13 (2114 hom., cov: 33)
  • Exomes 𝑓: 0.12 (8354 hom.)
• Consequence: RIC8A NM_001286134.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIC8A	NM_001286134.2	c.*194C>T		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.*194C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_001286134.2	ENSP00000432008.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19712 AN: 152122 Hom.: 2109 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0675

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.177 AC: 21474 AN: 121140 Hom.: 3418 AF XY: 0.170 AC XY: 11078 AN XY: 65146

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.0425

Gnomad EAS exome AF: 0.601

Gnomad SAS exome AF: 0.162

Gnomad FIN exome AF: 0.0384

Gnomad NFE exome AF: 0.0730

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.121 AC: 68052 AN: 560700 Hom.: 8354 Cov.: 6 AF XY: 0.121 AC XY: 36469 AN XY: 300338

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.0483

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.0428

Gnomad4 NFE exome AF: 0.0697

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.130 AC: 19746 AN: 152240 Hom.: 2114 Cov.: 33 AF XY: 0.133 AC XY: 9865 AN XY: 74446

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.0446

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.0675

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0817 Hom.: 623

Bravo AF: 0.150

Asia WGS AF: 0.335 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10081; hg19: chr11-214544; COSMIC: COSV57342833; COSMIC: COSV57342833;