chr1-110947994-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018372.4(LRIF1):c.2275C>A(p.Leu759Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
LRIF1
NM_018372.4 missense
NM_018372.4 missense
Scores
4
7
8
Clinical Significance
Conservation
PhyloP100: 3.90
Genes affected
LRIF1 (HGNC:30299): (ligand dependent nuclear receptor interacting factor 1) Predicted to enable retinoic acid receptor binding activity. Involved in dosage compensation by inactivation of X chromosome. Located in Barr body; centriolar satellite; and nucleoplasm. Colocalizes with chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRIF1 | NM_018372.4 | c.2275C>A | p.Leu759Ile | missense_variant | 4/4 | ENST00000369763.5 | |
LRIF1 | NM_001006945.2 | c.667C>A | p.Leu223Ile | missense_variant | 3/3 | ||
LRIF1 | XM_005271029.5 | c.2272C>A | p.Leu758Ile | missense_variant | 4/4 | ||
LRIF1 | XM_017001769.3 | c.1869+1857C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRIF1 | ENST00000369763.5 | c.2275C>A | p.Leu759Ile | missense_variant | 4/4 | 5 | NM_018372.4 | P1 | |
ENST00000440689.1 | n.1694+2834G>T | intron_variant, non_coding_transcript_variant | 2 | ||||||
LRIF1 | ENST00000485275.2 | c.667C>A | p.Leu223Ile | missense_variant | 3/3 | 2 | |||
LRIF1 | ENST00000494675.5 | c.667C>A | p.Leu223Ile | missense_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | May 04, 2022 | The c.2275C>A (p.L759I) alteration is located in exon 4 (coding exon 4) of the LRIF1 gene. This alteration results from a C to A substitution at nucleotide position 2275, causing the leucine (L) at amino acid position 759 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Gain of methylation at K764 (P = 0.098);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.