18-42804684-C-G

Variant names:

• chr18-42804684-C-G
• rs10502798
• NM_002930.4:c.427-60964G>C

Variant summary

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

The NM_002930.4(RIT2):​c.427-60964G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 151,990 control chromosomes in the GnomAD database, including 744 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 0.056 (744 hom., cov: 31)
• Consequence: RIT2 NM_002930.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002930.4. 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
	RIT2	NM_002930.4	MANE Select	c.427-60964G>C		intron	N/A	NP_002921.1
	RIT2	NM_001272077.2		c.*29-60964G>C		intron	N/A	NP_001259006.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIT2	ENST00000326695.10	TSL:1 MANE Select	c.427-60964G>C		intron	N/A	ENSP00000321805.4
	RIT2	ENST00000589109.5	TSL:1	c.*29-60964G>C		intron	N/A	ENSP00000467217.1
	RIT2	ENST00000590910.1	TSL:5	c.489-60964G>C		intron	N/A	ENSP00000466620.1

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8494 AN: 151874 Hom.: 745 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.0422

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

GnomAD4 genome AF: 0.0561 AC: 8522 AN: 151990 Hom.: 744 Cov.: 31 AF XY: 0.0543 AC XY: 4032 AN XY: 74290

African (AFR) AF: 0.190 AC: 7855 AN: 41392

American (AMR) AF: 0.0267 AC: 408 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00191 AC: 130 AN: 67992

Other (OTH) AF: 0.0418 AC: 88 AN: 2106

Alfa AF: 0.000848 Hom.: 0

Bravo AF: 0.0646

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.44
PhyloP100		-0.14
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: rs10502798; hg19: chr18-40384649;