rs16977065

Variant names:

• chr18-42857686-C-T
• rs16977065
• NM_002930.4:c.426+65886G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 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.426+65886G>A		intron	N/A	NP_002921.1
	RIT2	NM_001272077.2		c.*28+63011G>A		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.426+65886G>A		intron	N/A	ENSP00000321805.4
	RIT2	ENST00000589109.5	TSL:1	c.*28+63011G>A		intron	N/A	ENSP00000467217.1
	RIT2	ENST00000590910.1	TSL:5	c.488+65886G>A		intron	N/A	ENSP00000466620.1

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

African (AFR) AF: 0.00385 AC: 160 AN: 41566

American (AMR) AF: 0.105 AC: 1603 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1241 AN: 5162

South Asian (SAS) AF: 0.0721 AC: 348 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00184 AC: 125 AN: 68018

Other (OTH) AF: 0.0332 AC: 70 AN: 2110

Alfa AF: 0.0178 Hom.: 585

Bravo AF: 0.0318

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.94
DANN	Benign	0.73
PhyloP100		-0.51
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: rs16977065; hg19: chr18-40437651;