chr2-151414845-C-T

Variant summary

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

The NM_018151.5(RIF1):​c.206C>T​(p.Ser69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000082 in 1,610,056 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

RIF1
NM_018151.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.669
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]

Genome browser will be placed here

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=0.028603971).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RIF1NM_018151.5 linkuse as main transcriptc.206C>T p.Ser69Leu missense_variant 4/36 ENST00000444746.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RIF1ENST00000444746.7 linkuse as main transcriptc.206C>T p.Ser69Leu missense_variant 4/361 NM_018151.5 P2Q5UIP0-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152078
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000140
AC:
35
AN:
249490
Hom.:
0
AF XY:
0.000148
AC XY:
20
AN XY:
134724
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000176
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000547
Gnomad SAS exome
AF:
0.000536
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000972
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000878
AC:
128
AN:
1457860
Hom.:
0
Cov.:
29
AF XY:
0.0000966
AC XY:
70
AN XY:
724984
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000203
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000505
Gnomad4 SAS exome
AF:
0.000482
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000667
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152196
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000901
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.000157
AC:
19
Asia WGS
AF:
0.000289
AC:
1
AN:
3476

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 GeneticsJun 11, 2021The c.206C>T (p.S69L) alteration is located in exon 4 (coding exon 3) of the RIF1 gene. This alteration results from a C to T substitution at nucleotide position 206, causing the serine (S) at amino acid position 69 to be replaced by a leucine (L). 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
0.080
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
20
DANN
Benign
0.90
DEOGEN2
Benign
0.29
T;.;.;T;.
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.70
D
LIST_S2
Uncertain
0.87
.;.;.;D;D
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.029
T;T;T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
0.97
L;L;L;L;L
MutationTaster
Benign
0.70
D;D;D;D;D;D
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-2.8
D;D;D;D;D
REVEL
Benign
0.10
Sift
Benign
0.11
T;T;T;T;T
Sift4G
Benign
0.13
T;T;T;T;T
Polyphen
0.17
B;B;B;B;B
Vest4
0.17
MVP
0.27
MPC
0.042
ClinPred
0.032
T
GERP RS
1.7
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.061
gMVP
0.29

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: rs192238663; hg19: chr2-152271359; COSMIC: COSV54625215; API