11-214544-C-T

Variant names:

• chr11-214544-C-T
• rs10081
• NM_001286134.2:c.*194C>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.*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
• Publications: 14 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=-0.81).
• 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

GnomAD2 exomes AF: 0.177 AC: 21474 AN: 121140 AF XY: 0.170

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 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

African (AFR) AF: 0.167 AC: 2644 AN: 15788

American (AMR) AF: 0.266 AC: 8777 AN: 32944

Ashkenazi Jewish (ASJ) AF: 0.0483 AC: 882 AN: 18264

East Asian (EAS) AF: 0.537 AC: 16957 AN: 31564

South Asian (SAS) AF: 0.164 AC: 9750 AN: 59296

European-Finnish (FIN) AF: 0.0428 AC: 1356 AN: 31668

Middle Eastern (MID) AF: 0.0848 AC: 340 AN: 4008

European-Non Finnish (NFE) AF: 0.0697 AC: 23471 AN: 336776

Other (OTH) AF: 0.128 AC: 3875 AN: 30392

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

African (AFR) AF: 0.172 AC: 7155 AN: 41544

American (AMR) AF: 0.219 AC: 3354 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 155 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2946 AN: 5180

South Asian (SAS) AF: 0.168 AC: 810 AN: 4824

European-Finnish (FIN) AF: 0.0417 AC: 442 AN: 10612

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0675 AC: 4587 AN: 68000

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.0967 Hom.: 2885

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
PhyloP100		0.0080
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: rs10081; hg19: chr11-214544; COSMIC: COSV57342833; COSMIC: COSV57342833;