rs9948019

Variant names:

• chr18-43080133-A-G
• rs9948019
• NM_002930.4:c.103+35284T>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.103+35284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,090 control chromosomes in the GnomAD database, including 1,873 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 0.15 (1873 hom., cov: 32)
• Consequence: RIT2 NM_002930.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIT2	NM_002930.4	c.103+35284T>C		intron_variant	Intron 1 of 4	ENST00000326695.10	NP_002921.1
RIT2	NM_001272077.2	c.103+35284T>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+35284T>C		intron_variant	Intron 1 of 4	1	NM_002930.4	ENSP00000321805.4
RIT2	ENST00000589109.5	c.103+35284T>C		intron_variant	Intron 1 of 5	1		ENSP00000467217.1
RIT2	ENST00000590910.1	c.103+35284T>C		intron_variant	Intron 1 of 5	5		ENSP00000466620.1
RIT2	ENST00000650392.1	n.103+35284T>C		intron_variant	Intron 1 of 6			ENSP00000497708.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23052 AN: 151972 Hom.: 1871 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.152 AC: 23068 AN: 152090 Hom.: 1873 Cov.: 32 AF XY: 0.153 AC XY: 11396 AN XY: 74360

African (AFR) AF: 0.147 AC: 6098 AN: 41490

American (AMR) AF: 0.129 AC: 1976 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3466

East Asian (EAS) AF: 0.00560 AC: 29 AN: 5178

South Asian (SAS) AF: 0.207 AC: 999 AN: 4816

European-Finnish (FIN) AF: 0.201 AC: 2131 AN: 10578

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10661 AN: 67966

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.164 Hom.: 595

Bravo AF: 0.144

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.70
PhyloP100		2.6
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: rs9948019; hg19: chr18-40660098;