2-151416814-G-T

Variant names:

• chr2-151416814-G-T
• NM_018151.5:c.416G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018151.5(RIF1):​c.416G>T​(p.Ser139Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RIF1 NM_018151.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842

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

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=0.15486369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIF1	NM_018151.5	c.416G>T	p.Ser139Ile	missense_variant	Exon 6 of 36	ENST00000444746.7	NP_060621.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIF1	ENST00000444746.7	c.416G>T	p.Ser139Ile	missense_variant	Exon 6 of 36	1	NM_018151.5	ENSP00000390181.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457508 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724912

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;.;.;T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.77	.;.;.;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M;M;M;M;M
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D
REVEL	Benign	0.11
Sift	Uncertain	0.022	D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D
Polyphen		0.85	P;P;P;P;P
Vest4		0.41
MutPred		0.40		Gain of methylation at K135 (P = 0.0703);Gain of methylation at K135 (P = 0.0703);Gain of methylation at K135 (P = 0.0703);Gain of methylation at K135 (P = 0.0703);Gain of methylation at K135 (P = 0.0703);
MVP		0.43
MPC		0.078
ClinPred		0.77	D
GERP RS		-0.49
Varity_R		0.13
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr2-152273328;