rs16977065

Positions:

• chr18-42857686-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.426+65886G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 152,262 control chromosomes in the GnomAD database, including 287 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 0.023 (287 hom., cov: 32)
• Consequence: RIT2 NM_002930.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIT2	NM_002930.4	c.426+65886G>A		intron_variant		ENST00000326695.10
RIT2	NM_001272077.2	c.*28+63011G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIT2	ENST00000326695.10	c.426+65886G>A		intron_variant		1	NM_002930.4	P1
RIT2	ENST00000589109.5	c.*28+63011G>A		intron_variant		1
RIT2	ENST00000590910.1	c.488+65886G>A		intron_variant		5
RIT2	ENST00000650392.1	c.*56-12517G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3553 AN: 152146 Hom.: 286 Cov.: 32

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.0718

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00182

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0234 AC: 3563 AN: 152262 Hom.: 287 Cov.: 32 AF XY: 0.0270 AC XY: 2009 AN XY: 74444

Gnomad4 AFR AF: 0.00385

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.0721

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00184

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.0155 Hom.: 328

Bravo AF: 0.0318

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.94
DANN	Benign	0.73

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: rs16977065; hg19: chr18-40437651;