chr20-19886612-C-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_018993.4(RIN2):c.-36-2954C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.015 ( 62 hom., cov: 16)
Exomes 𝑓: 0.00038 ( 0 hom. )
Consequence
RIN2
NM_018993.4 intron
NM_018993.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.852
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 20-19886612-C-T is Benign according to our data. Variant chr20-19886612-C-T is described in ClinVar as [Benign]. Clinvar id is 1228223.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| RIN2 | NM_018993.4 | c.-36-2954C>T | intron_variant | ENST00000255006.12 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RIN2 | ENST00000255006.12 | c.-36-2954C>T | intron_variant | 2 | NM_018993.4 | P1 | |||
| RIN2 | ENST00000648440.1 | c.-205C>T | 5_prime_UTR_variant | 1/12 | P1 | ||||
| RIN2 | ENST00000432334.2 | n.537-2954C>T | intron_variant, non_coding_transcript_variant | 4 | |||||
| RIN2 | ENST00000648165.1 | n.618-2954C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes 0.0150 AC: 1731AN: 115190Hom.: 61 Cov.: 16
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GnomAD4 exome AF: 0.000382 AC: 155AN: 405554Hom.: 0 Cov.: 6 AF XY: 0.000374 AC XY: 82AN XY: 219132
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GnomAD4 genome 0.0150 AC: 1732AN: 115178Hom.: 62 Cov.: 16 AF XY: 0.0147 AC XY: 796AN XY: 54180
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
| Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 08, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at