rs757397798

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004292.3(RIN1):​c.2336G>T​(p.Arg779Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R779Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RIN1
NM_004292.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.96
Variant links:
Genes affected
RIN1 (HGNC:18749): (Ras and Rab interactor 1) Predicted to enable small GTPase binding activity. Predicted to be involved in endocytosis; regulation of catalytic activity; and signal transduction. Predicted to act upstream of or within associative learning; memory; and negative regulation of synaptic plasticity. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03382352).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RIN1NM_004292.3 linkc.2336G>T p.Arg779Leu missense_variant Exon 10 of 10 ENST00000311320.9 NP_004283.2 Q13671-1A0A0S2Z4U0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RIN1ENST00000311320.9 linkc.2336G>T p.Arg779Leu missense_variant Exon 10 of 10 1 NM_004292.3 ENSP00000310406.4 Q13671-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461698
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
727166
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.011
DANN
Benign
0.66
DEOGEN2
Benign
0.11
T;.
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.3
FATHMM_MKL
Benign
0.0056
N
LIST_S2
Benign
0.62
T;T
M_CAP
Benign
0.0058
T
MetaRNN
Benign
0.034
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.55
N;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.71
N;N
REVEL
Benign
0.0060
Sift
Benign
0.27
T;T
Sift4G
Benign
0.32
T;T
Polyphen
0.0
B;B
Vest4
0.080
MutPred
0.23
Loss of solvent accessibility (P = 0.0606);.;
MVP
0.040
MPC
0.32
ClinPred
0.049
T
GERP RS
-8.9
Varity_R
0.028
gMVP
0.082

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs757397798; hg19: chr11-66099763; API