rs1749409

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006912.6(RIT1):c.430-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 1,613,008 control chromosomes in the GnomAD database, including 662,209 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 52278 hom., cov: 32)

Exomes 𝑓: 0.91 ( 609931 hom. )

Consequence

RIT1
NM_006912.6 splice_region, intron

Scores

Splicing: ADA: 0.00001202

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.987

Variant links:

Genes affected

RIT1 (HGNC:10023): (Ras like without CAAX 1) This gene encodes a member of a subfamily of Ras-related GTPases. The encoded protein is involved in regulating p38 MAPK-dependent signaling cascades related to cellular stress. This protein also cooperates with nerve growth factor to promote neuronal development and regeneration. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

RIT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-155900625-G-A is Benign according to our data. Variant chr1-155900625-G-A is described in ClinVar as [Benign]. Clinvar id is 181519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-155900625-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RIT1	NM_006912.6 link	c.430-7C>T	splice_region_variant, intron_variant	Intron 5 of 5	ENST00000368323.8	NP_008843.1	Q92963-1
RIT1	NM_001256821.2 link	c.481-7C>T	splice_region_variant, intron_variant	Intron 5 of 5		NP_001243750.1	Q92963-3
RIT1	NM_001256820.2 link	c.322-7C>T	splice_region_variant, intron_variant	Intron 4 of 4		NP_001243749.1	Q92963-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIT1	ENST00000368323.8 link	c.430-7C>T		splice_region_variant, intron_variant	Intron 5 of 5	1	NM_006912.6	ENSP00000357306.3		Q92963-1

Frequencies

GnomAD3 genomes

AF:

0.812

AC:

123461

AN:

152038

Hom.:

52266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.779

Gnomad AMR

AF:

0.907

Gnomad ASJ

AF:

0.875

Gnomad EAS

AF:

0.939

Gnomad SAS

AF:

0.865

Gnomad FIN

AF:

0.890

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.925

Gnomad OTH

AF:

0.844

GnomAD3 exomes

AF:

0.886

AC:

222070

AN:

250514

Hom.:

99654

AF XY:

0.889

AC XY:

120380

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.533

Gnomad AMR exome

AF:

0.945

Gnomad ASJ exome

AF:

0.874

Gnomad EAS exome

AF:

0.940

Gnomad SAS exome

AF:

0.856

Gnomad FIN exome

AF:

0.888

Gnomad NFE exome

AF:

0.920

Gnomad OTH exome

AF:

0.890

GnomAD4 exome

AF:

0.911

AC:

1331394

AN:

1460852

Hom.:

609931

Cov.:

AF XY:

0.910

AC XY:

661582

AN XY:

726698

show subpopulations

Gnomad4 AFR exome

AF:

0.528

Gnomad4 AMR exome

AF:

0.941

Gnomad4 ASJ exome

AF:

0.877

Gnomad4 EAS exome

AF:

0.945

Gnomad4 SAS exome

AF:

0.856

Gnomad4 FIN exome

AF:

0.894

Gnomad4 NFE exome

AF:

0.928

Gnomad4 OTH exome

AF:

0.891

GnomAD4 genome

AF:

0.812

AC:

123492

AN:

152156

Hom.:

52278

Cov.:

AF XY:

0.813

AC XY:

60483

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.542

Gnomad4 AMR

AF:

0.907

Gnomad4 ASJ

AF:

0.875

Gnomad4 EAS

AF:

0.939

Gnomad4 SAS

AF:

0.866

Gnomad4 FIN

AF:

0.890

Gnomad4 NFE

AF:

0.925

Gnomad4 OTH

AF:

0.844

Alfa

AF:

0.902

Hom.:

124151

Bravo

AF:

0.802

Asia WGS

AF:

0.875

AC:

3043

AN:

3478

EpiCase

AF:

0.918

EpiControl

AF:

0.921

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Aug 17, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

481-7C>T in intron 5 of RIT1: This variant is not expected to have clinical sign ificance because it has been identified in 45.4% (2001/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs1749409). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Noonan syndrome 8

Benign:2

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jul 04, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The RIT1 c.430-7C>T variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 106445/121348 control chromosomes (47428 homozygotes) at a frequency of 0.8771879, which is approximately 70175 times the estimated maximal expected allele frequency of a pathogenic RIT1 variant (0.0000125), therefore it is a very common polymorphism found in general population. Based on the allele frequency of this variant in general population, it is classified as benign. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.5

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over