rs7226659

Positions:

• chr18-42908314-G-T

Variant summary

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

The NM_002930.4(RIT2):​c.426+15258C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 152,054 control chromosomes in the GnomAD database, including 1,299 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 0.068 (1299 hom., cov: 32)
• Consequence: RIT2 NM_002930.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIT2	NM_002930.4	c.426+15258C>A		intron_variant		ENST00000326695.10	NP_002921.1
RIT2	NM_001272077.2	c.*28+12383C>A		intron_variant			NP_001259006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIT2	ENST00000326695.10	c.426+15258C>A		intron_variant		1	NM_002930.4	ENSP00000321805	P1
RIT2	ENST00000589109.5	c.*28+12383C>A		intron_variant		1		ENSP00000467217
RIT2	ENST00000590910.1	c.488+15258C>A		intron_variant		5		ENSP00000466620
RIT2	ENST00000650392.1	c.489-4471C>A		intron_variant, NMD_transcript_variant				ENSP00000497708

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10354 AN: 151936 Hom.: 1283 Cov.: 32

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0675

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0529

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.0722

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

GnomAD4 genome AF: 0.0683 AC: 10381 AN: 152054 Hom.: 1299 Cov.: 32 AF XY: 0.0741 AC XY: 5507 AN XY: 74328

Gnomad4 AFR AF: 0.0379

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0675

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0529

Gnomad4 NFE AF: 0.0288

Gnomad4 OTH AF: 0.0843

Alfa AF: 0.0395 Hom.: 397

Bravo AF: 0.0768

Asia WGS AF: 0.369 AC: 1277 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.39

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: rs7226659; hg19: chr18-40488279;