rs10444533

Variant names:

• chr12-106835927-C-T
• rs10444533
• NM_001330145.2:c.837-6662C>T

Variant summary

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

The NM_001330145.2(RIC8B):​c.837-6662C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,184 control chromosomes in the GnomAD database, including 2,932 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 0.19 (2932 hom., cov: 32)
• Consequence: RIC8B NM_001330145.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830
• Publications: 9 publications found

Genes affected

RIC8B (HGNC:25555): (RIC8 guanine nucleotide exchange factor B) Enables G-protein alpha-subunit binding activity. Acts upstream of or within regulation of G protein-coupled receptor signaling pathway. Located in cytosol 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330145.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIC8B	NM_001330145.2	MANE Select	c.837-6662C>T		intron	N/A	NP_001317074.1
	RIC8B	NM_001351361.2		c.813-6662C>T		intron	N/A	NP_001338290.1
	RIC8B	NM_001330146.2		c.789-6662C>T		intron	N/A	NP_001317075.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIC8B	ENST00000392837.9	TSL:5 MANE Select	c.837-6662C>T		intron	N/A	ENSP00000376582.4
	RIC8B	ENST00000392839.6	TSL:1	c.837-6662C>T		intron	N/A	ENSP00000376583.2
	RIC8B	ENST00000355478.6	TSL:1	c.717-6662C>T		intron	N/A	ENSP00000347662.2

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28791 AN: 152066 Hom.: 2934 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.184

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.189 AC: 28802 AN: 152184 Hom.: 2932 Cov.: 32 AF XY: 0.189 AC XY: 14078 AN XY: 74402

African (AFR) AF: 0.111 AC: 4604 AN: 41538

American (AMR) AF: 0.216 AC: 3303 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 432 AN: 3468

East Asian (EAS) AF: 0.315 AC: 1631 AN: 5174

South Asian (SAS) AF: 0.248 AC: 1197 AN: 4822

European-Finnish (FIN) AF: 0.177 AC: 1878 AN: 10590

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15129 AN: 67980

Other (OTH) AF: 0.181 AC: 382 AN: 2112

Alfa AF: 0.215 Hom.: 7032

Bravo AF: 0.192

Asia WGS AF: 0.249 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.55
PhyloP100		0.83
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: rs10444533; hg19: chr12-107229705;