rs10502799

Positions:

• chr18-42811721-C-T

Variant summary

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

The NM_002930.4(RIT2):​c.427-68001G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0728 in 151,820 control chromosomes in the GnomAD database, including 1,280 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 0.073 (1280 hom., cov: 32)
• Consequence: RIT2 NM_002930.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

Genes affected

RIT2 (HGNC:10017): (Ras like without CAAX 2) RIN belongs to the RAS (HRAS; MIM 190020) superfamily of small GTPases (Shao et al., 1999 [PubMed 10545207]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIT2	NM_002930.4	c.427-68001G>A		intron_variant		ENST00000326695.10	NP_002921.1
RIT2	NM_001272077.2	c.*29-68001G>A		intron_variant			NP_001259006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIT2	ENST00000326695.10	c.427-68001G>A		intron_variant		1	NM_002930.4	ENSP00000321805.4
RIT2	ENST00000589109.5	c.*29-68001G>A		intron_variant		1		ENSP00000467217.1
RIT2	ENST00000590910.1	c.489-68001G>A		intron_variant		5		ENSP00000466620.1

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11025 AN: 151702 Hom.: 1279 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00202

Gnomad OTH AF: 0.0571

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

GnomAD4 genome AF: 0.0728 AC: 11060 AN: 151820 Hom.: 1280 Cov.: 32 AF XY: 0.0704 AC XY: 5226 AN XY: 74196

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00202

Gnomad4 OTH AF: 0.0565

Alfa AF: 0.0388 Hom.: 170

Bravo AF: 0.0830

Asia WGS AF: 0.0210 AC: 73 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.5
DANN	Benign	0.75

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: rs10502799; hg19: chr18-40391686;