GeneBe

rs11362637

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018993.4(RIN2):​c.-36-2945_-36-2935delTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000768 in 520,974 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000017 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

RIN2
NM_018993.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.204

Publications

2 publications found
Variant links:
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]
RIN2 Gene-Disease associations (from GenCC):
  • RIN2 syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018993.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RIN2
NM_018993.4
MANE Select
c.-36-2945_-36-2935delTTTTTTTTTTT
intron
N/ANP_061866.1Q8WYP3-1
RIN2
NM_001378238.1
c.-581-2945_-581-2935delTTTTTTTTTTT
intron
N/ANP_001365167.1
RIN2
NM_001242581.2
c.-57_-47delTTTTTTTTTTT
upstream_gene
N/ANP_001229510.1Q8WYP3-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RIN2
ENST00000255006.12
TSL:2 MANE Select
c.-36-2945_-36-2935delTTTTTTTTTTT
intron
N/AENSP00000255006.7Q8WYP3-1
RIN2
ENST00000648440.1
c.-196_-186delTTTTTTTTTTT
5_prime_UTR
Exon 1 of 12ENSP00000498085.1Q8WYP3-1
RIN2
ENST00000944201.1
c.-196_-186delTTTTTTTTTTT
5_prime_UTR
Exon 1 of 10ENSP00000614260.1

Frequencies

GnomAD3 genomes
AF:
0.0000173
AC:
2
AN:
115278
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000681
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000493
AC:
2
AN:
405696
Hom.:
0
AF XY:
0.00000912
AC XY:
2
AN XY:
219210
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
8542
American (AMR)
AF:
0.00
AC:
0
AN:
16344
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
12956
East Asian (EAS)
AF:
0.0000410
AC:
1
AN:
24372
South Asian (SAS)
AF:
0.00
AC:
0
AN:
40326
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
32824
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2328
European-Non Finnish (NFE)
AF:
0.00000406
AC:
1
AN:
246514
Other (OTH)
AF:
0.00
AC:
0
AN:
21490
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.0000173
AC:
2
AN:
115278
Hom.:
0
Cov.:
0
AF XY:
0.0000185
AC XY:
1
AN XY:
54192
show subpopulations
African (AFR)
AF:
0.0000681
AC:
2
AN:
29384
American (AMR)
AF:
0.00
AC:
0
AN:
10898
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3012
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4074
South Asian (SAS)
AF:
0.00
AC:
0
AN:
3414
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
4676
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
226
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
57268
Other (OTH)
AF:
0.00
AC:
0
AN:
1532
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.650
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs11362637; hg19: chr20-19867256; API