rs10444533

chr12-106835927-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIC8B	NM_001330145.2	c.837-6662C>T		intron_variant		ENST00000392837.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIC8B	ENST00000392837.9	c.837-6662C>T		intron_variant		5	NM_001330145.2	P1

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

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.181

Alfa AF: 0.218 Hom.: 5242

Bravo AF: 0.192

Asia WGS AF: 0.249 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.0
Dann	Benign	0.55

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: rs10444533; hg19: chr12-107229705;