18-43098270-T-C

Variant names:

• chr18-43098270-T-C
• rs4130047
• NM_002930.4:c.103+17147A>G

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+17147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,700 control chromosomes in the GnomAD database, including 7,924 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 0.32 (7924 hom., cov: 32)
• Consequence: RIT2 NM_002930.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.31
• Publications: 21 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIT2	NM_002930.4	c.103+17147A>G		intron_variant	Intron 1 of 4	ENST00000326695.10	NP_002921.1
RIT2	NM_001272077.2	c.103+17147A>G		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+17147A>G		intron_variant	Intron 1 of 4	1	NM_002930.4	ENSP00000321805.4
RIT2	ENST00000589109.5	c.103+17147A>G		intron_variant	Intron 1 of 5	1		ENSP00000467217.1
RIT2	ENST00000590910.1	c.103+17147A>G		intron_variant	Intron 1 of 5	5		ENSP00000466620.1
RIT2	ENST00000650392.1	n.103+17147A>G		intron_variant	Intron 1 of 6			ENSP00000497708.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48816 AN: 151582 Hom.: 7911 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.322 AC: 48869 AN: 151700 Hom.: 7924 Cov.: 32 AF XY: 0.325 AC XY: 24085 AN XY: 74112

African (AFR) AF: 0.287 AC: 11916 AN: 41466

American (AMR) AF: 0.374 AC: 5681 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3462

East Asian (EAS) AF: 0.378 AC: 1942 AN: 5132

South Asian (SAS) AF: 0.318 AC: 1531 AN: 4812

European-Finnish (FIN) AF: 0.369 AC: 3899 AN: 10554

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21695 AN: 67780

Other (OTH) AF: 0.317 AC: 667 AN: 2104

Alfa AF: 0.316 Hom.: 27245

Bravo AF: 0.321

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.016
DANN	Benign	0.31
PhyloP100		-4.3
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: rs4130047; hg19: chr18-40678235;