rs1749409
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, splice polypyrimidine tract, 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
Consequence
NM_006912.6 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIT1 | NM_006912.6 | c.430-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000368323.8 | |||
RIT1 | NM_001256820.2 | c.322-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
RIT1 | NM_001256821.2 | c.481-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIT1 | ENST00000368323.8 | c.430-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006912.6 | P3 |
Frequencies
GnomAD3 genomes AF: 0.812 AC: 123461AN: 152038Hom.: 52266 Cov.: 32
GnomAD3 exomes AF: 0.886 AC: 222070AN: 250514Hom.: 99654 AF XY: 0.889 AC XY: 120380AN XY: 135402
GnomAD4 exome AF: 0.911 AC: 1331394AN: 1460852Hom.: 609931 Cov.: 37 AF XY: 0.910 AC XY: 661582AN XY: 726698
GnomAD4 genome AF: 0.812 AC: 123492AN: 152156Hom.: 52278 Cov.: 32 AF XY: 0.813 AC XY: 60483AN XY: 74392
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | 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). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 17, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Noonan syndrome 8 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 04, 2017 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at