Variant 2-151410455-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018151.5(RIF1):c.32C>A(p.Pro11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,742 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: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RIF1
NM_018151.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33222133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIF1	NM_018151.5 link	c.32C>A	p.Pro11Gln	missense_variant	Exon 2 of 36	ENST00000444746.7	NP_060621.3	Q5UIP0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIF1	ENST00000444746.7 link	c.32C>A	p.Pro11Gln	missense_variant	Exon 2 of 36	1	NM_018151.5	ENSP00000390181.2		Q5UIP0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250066

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135240

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.32C>A (p.P11Q) alteration is located in exon 2 (coding exon 1) of the RIF1 gene. This alteration results from a C to A substitution at nucleotide position 32, causing the proline (P) at amino acid position 11 to be replaced by a glutamine (Q). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.47

T;.;.;T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.79

.;.;.;T;T

M_CAP

Benign

0.050

MetaRNN

Benign

0.33

T;T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.6

M;M;M;M;M

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.2

D;D;D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;D;D;D;D

Vest4

0.52

MutPred

0.15

Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);

MVP

0.35

MPC

0.30

ClinPred

0.97

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.57

gMVP

0.39

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