chr2-151437250-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018151.5(RIF1):ā€‹c.1382A>Gā€‹(p.Glu461Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RIF1
NM_018151.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66
Variant links:
Genes affected
RIF1 (HGNC:23207): (replication timing regulatory factor 1) This gene encodes a protein that shares homology with the yeast teleomere binding protein, Rap1 interacting factor 1. This protein localizes to aberrant telomeres may be involved in DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26168185).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RIF1NM_018151.5 linkuse as main transcriptc.1382A>G p.Glu461Gly missense_variant 13/36 ENST00000444746.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RIF1ENST00000444746.7 linkuse as main transcriptc.1382A>G p.Glu461Gly missense_variant 13/361 NM_018151.5 P2Q5UIP0-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1457798
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
725480
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 02, 2021The c.1382A>G (p.E461G) alteration is located in exon 13 (coding exon 12) of the RIF1 gene. This alteration results from a A to G substitution at nucleotide position 1382, causing the glutamic acid (E) at amino acid position 461 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.31
T;.;.;T;.
Eigen
Benign
0.12
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.91
.;.;.;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.26
T;T;T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
1.8
L;L;L;L;L
MutationTaster
Benign
1.0
D;N;N;N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-3.2
D;D;D;D;D
REVEL
Benign
0.083
Sift
Uncertain
0.025
D;D;D;D;D
Sift4G
Uncertain
0.022
D;D;D;D;D
Polyphen
0.85
P;D;D;P;D
Vest4
0.47
MutPred
0.37
Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP
0.20
MPC
0.18
ClinPred
0.83
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.11
gMVP
0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-152293764; API