Variant chr2-151436851-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018151.5(RIF1):c.1220C>T(p.Pro407Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000696 in 1,609,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

RIF1
NM_018151.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

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]

RIF1 links:

RIF1 (HGNC:):

RIF1 links:

Genome browser will be placed here

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=0.11783382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIF1	NM_018151.5 linkuse as main transcript	c.1220C>T	p.Pro407Leu	missense_variant	12/36	ENST00000444746.7	NP_060621.3	Q5UIP0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIF1	ENST00000444746.7 linkuse as main transcript	c.1220C>T	p.Pro407Leu	missense_variant	12/36	1	NM_018151.5	ENSP00000390181.2		Q5UIP0-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

151760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000805

AC:

AN:

248586

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

134466

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000624

AC:

AN:

1458020

Hom.:

Cov.:

AF XY:

0.0000869

AC XY:

AN XY:

725326

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000936

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000631

Gnomad4 OTH exome

AF:

0.0000997

GnomAD4 genome

AF:

0.000138

AC:

AN:

151876

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000766

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000165

EpiControl

AF:

0.000119

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 submitter

clinical testing

Ambry Genetics

Apr 27, 2024

The c.1220C>T (p.P407L) alteration is located in exon 12 (coding exon 11) of the RIF1 gene. This alteration results from a C to T substitution at nucleotide position 1220, causing the proline (P) at amino acid position 407 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

0.073

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

T;.;.;T;.

Eigen

Benign

0.036

Eigen_PC

Benign

-0.0041

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

.;.;.;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.4

M;M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;N

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.4

D;D;D;D;D

REVEL

Benign

0.099

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

0.94

P;P;P;P;P

Vest4

0.23

MVP

0.17

MPC

0.18

ClinPred

0.36

GERP RS

5.7

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.14

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over