rs12456492

chr18-43093415-A-Gchr18-43093415-A-T

Variant summary

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

The NM_002930.4(RIT2):c.103+22002T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,938 control chromosomes in the GnomAD database, including 8,201 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 0.33 (8201 hom., cov: 32)
• Consequence: RIT2 NM_002930.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIT2	NM_002930.4	c.103+22002T>C		intron_variant		ENST00000326695.10
RIT2	NM_001272077.2	c.103+22002T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIT2	ENST00000326695.10	c.103+22002T>C		intron_variant		1	NM_002930.4	P1
RIT2	ENST00000589109.5	c.103+22002T>C		intron_variant		1
RIT2	ENST00000590910.1	c.103+22002T>C		intron_variant		5
RIT2	ENST00000650392.1	c.103+22002T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49728 AN: 151820 Hom.: 8186 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.328 AC: 49786 AN: 151938 Hom.: 8201 Cov.: 32 AF XY: 0.331 AC XY: 24558 AN XY: 74262

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.314

Alfa AF: 0.324 Hom.: 4721

Bravo AF: 0.327

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	3.8
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: rs12456492; hg19: chr18-40673380;