Variant 2-151428861-G-A 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.864G>A(p.Met288Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

RIF1
NM_018151.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

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:

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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=0.11743167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIF1	NM_018151.5 linkuse as main transcript	c.864G>A	p.Met288Ile	missense_variant	9/36	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.864G>A	p.Met288Ile	missense_variant	9/36	1	NM_018151.5	ENSP00000390181.2		Q5UIP0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.19e-7

AC:

AN:

1391594

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

696522

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:

9.54e-7

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.864G>A (p.M288I) alteration is located in exon 9 (coding exon 8) of the RIF1 gene. This alteration results from a G to A substitution at nucleotide position 864, causing the methionine (M) at amino acid position 288 to be replaced by an isoleucine (I). 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

0.17

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

T;.;.;T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.017

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

.;.;.;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;L;L;L;L

MutationTaster

Benign

0.94

N;N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.25

N;N;N;N;N

REVEL

Benign

0.081

Sift

Benign

0.20

T;T;T;T;T

Sift4G

Benign

0.36

T;T;T;T;T

Polyphen

0.0090

B;B;B;B;B

Vest4

0.17

MutPred

0.51

Gain of ubiquitination at K291 (P = 0.0832);Gain of ubiquitination at K291 (P = 0.0832);Gain of ubiquitination at K291 (P = 0.0832);Gain of ubiquitination at K291 (P = 0.0832);Gain of ubiquitination at K291 (P = 0.0832);

MVP

0.30

MPC

0.049

ClinPred

0.61

GERP RS

5.0

Varity_R

0.079

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over