2-151410455-C-T

Variant names:

• chr2-151410455-C-T
• rs1014018455
• NM_018151.5:c.32C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018151.5(RIF1):​c.32C>T​(p.Pro11Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RIF1 NM_018151.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34437078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIF1	NM_018151.5	c.32C>T	p.Pro11Leu	missense_variant	Exon 2 of 36	ENST00000444746.7	NP_060621.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIF1	ENST00000444746.7	c.32C>T	p.Pro11Leu	missense_variant	Exon 2 of 36	1	NM_018151.5	ENSP00000390181.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D;.;.;D;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.87	.;.;.;D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.34	T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.6	M;M;M;M;M
PhyloP100		3.5
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.2	D;D;D;D;D
REVEL	Benign	0.16
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		0.59
MutPred		0.23		Loss of loop (P = 0.0031);Loss of loop (P = 0.0031);Loss of loop (P = 0.0031);Loss of loop (P = 0.0031);Loss of loop (P = 0.0031);
MVP		0.30
MPC		0.31
ClinPred		0.99	D
GERP RS		4.0
PromoterAI		0.0084	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.52
gMVP		0.59
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs1014018455; hg19: chr2-152266969;