rs72242041
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_018993.4(RIN2):c.-36-2865del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,539,418 control chromosomes in the GnomAD database, including 200 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.021 ( 97 hom., cov: 29)
Exomes 𝑓: 0.0023 ( 103 hom. )
Consequence
RIN2
NM_018993.4 intron
NM_018993.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.244
Genes affected
RIN2 (HGNC:18750): (Ras and Rab interactor 2) The RAB5 protein is a small GTPase involved in membrane trafficking in the early endocytic pathway. The protein encoded by this gene binds the GTP-bound form of the RAB5 protein preferentially over the GDP-bound form, and functions as a guanine nucleotide exchange factor for RAB5. The encoded protein is found primarily as a tetramer in the cytoplasm and does not bind other members of the RAB family. Mutations in this gene cause macrocephaly alopecia cutis laxa and scoliosis (MACS) syndrome, an elastic tissue disorder, as well as the related connective tissue disorder, RIN2 syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 20-19886698-CT-C is Benign according to our data. Variant chr20-19886698-CT-C is described in ClinVar as [Benign]. Clinvar id is 445625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIN2 | NM_018993.4 | c.-36-2865del | intron_variant | ENST00000255006.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIN2 | ENST00000255006.12 | c.-36-2865del | intron_variant | 2 | NM_018993.4 | P1 | |||
RIN2 | ENST00000648440.1 | c.-116del | 5_prime_UTR_variant | 1/12 | P1 | ||||
RIN2 | ENST00000432334.2 | n.537-2865del | intron_variant, non_coding_transcript_variant | 4 | |||||
RIN2 | ENST00000648165.1 | n.618-2865del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0209 AC: 3093AN: 148220Hom.: 96 Cov.: 29
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GnomAD3 exomes AF: 0.00397 AC: 596AN: 150168Hom.: 21 AF XY: 0.00336 AC XY: 271AN XY: 80614
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GnomAD4 exome AF: 0.00230 AC: 3205AN: 1391094Hom.: 103 Cov.: 30 AF XY: 0.00206 AC XY: 1415AN XY: 686086
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GnomAD4 genome ? AF: 0.0209 AC: 3098AN: 148324Hom.: 97 Cov.: 29 AF XY: 0.0198 AC XY: 1427AN XY: 72064
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 30, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at