rs12456492

Variant names:

• chr18-43093415-A-G
• rs12456492
• NM_002930.4:c.103+22002T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-43093415-A-G
• chr18-43093415-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 63 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RIT2	NM_002930.4	c.103+22002T>C		intron_variant	Intron 1 of 4	ENST00000326695.10	NP_002921.1
RIT2	NM_001272077.2	c.103+22002T>C		intron_variant	Intron 1 of 5		NP_001259006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIT2	ENST00000326695.10	c.103+22002T>C		intron_variant	Intron 1 of 4	1	NM_002930.4	ENSP00000321805.4
RIT2	ENST00000589109.5	c.103+22002T>C		intron_variant	Intron 1 of 5	1		ENSP00000467217.1
RIT2	ENST00000590910.1	c.103+22002T>C		intron_variant	Intron 1 of 5	5		ENSP00000466620.1
RIT2	ENST00000650392.1	n.103+22002T>C		intron_variant	Intron 1 of 6			ENSP00000497708.1

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

African (AFR) AF: 0.306 AC: 12705 AN: 41464

American (AMR) AF: 0.371 AC: 5647 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1069 AN: 3464

East Asian (EAS) AF: 0.380 AC: 1956 AN: 5152

South Asian (SAS) AF: 0.319 AC: 1536 AN: 4818

European-Finnish (FIN) AF: 0.370 AC: 3912 AN: 10578

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21795 AN: 67936

Other (OTH) AF: 0.314 AC: 661 AN: 2106

Alfa AF: 0.324 Hom.: 19588

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
PhyloP100		0.68
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: rs12456492; hg19: chr18-40673380;