chr19-1272009-C-T

Variant summary

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

The NM_001300829.2(CIRBP):​c.460C>T​(p.Arg154Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,611,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CIRBP
NM_001300829.2 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61
Variant links:
Genes affected
CIRBP (HGNC:1982): (cold inducible RNA binding protein) Enables mRNA 3'-UTR binding activity and small ribosomal subunit rRNA binding activity. Involved in mRNA stabilization; positive regulation of translation; and response to UV. Located in cytoplasm and nucleoplasm. [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 rank MANE Protein UniProt
CIRBPNM_001300829.2 linkc.460C>T p.Arg154Trp missense_variant Exon 6 of 6 ENST00000587896.6 NP_001287758.1 Q14011D6W5Y5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CIRBPENST00000587896.6 linkc.460C>T p.Arg154Trp missense_variant Exon 6 of 6 2 NM_001300829.2 ENSP00000466025.1 D6W5Y5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250694
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135582
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000959
AC:
14
AN:
1459776
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
725722
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000991
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.460C>T (p.R154W) alteration is located in exon 6 (coding exon 5) of the CIRBP gene. This alteration results from a C to T substitution at nucleotide position 460, causing the arginine (R) at amino acid position 154 to be replaced by a tryptophan (W). 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
0.46
BayesDel_addAF
Uncertain
0.064
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T;T;T;.;T;T;T;T;.;T;T;.;T;T;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.19
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Pathogenic
0.98
.;.;.;.;D;.;.;D;.;.;.;D;.;D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Uncertain
0.47
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.7
M;M;M;.;.;M;.;.;.;.;.;.;.;M;.
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.8
.;.;.;.;.;.;.;.;.;.;.;D;.;D;.
REVEL
Benign
0.16
Sift
Pathogenic
0.0
.;.;.;.;.;.;.;.;.;.;.;D;.;D;.
Sift4G
Benign
0.17
T;T;T;T;T;T;D;D;T;D;D;D;D;T;T
Polyphen
0.0020
B;B;B;.;.;B;B;B;.;B;B;.;B;B;.
Vest4
0.76
MutPred
0.36
Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);.;Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);Loss of MoRF binding (P = 0.0962);
MVP
0.69
MPC
0.68
ClinPred
0.98
D
GERP RS
0.65
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
2.7
Varity_R
0.35
gMVP
0.71

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.

Other links and lift over

dbSNP: rs772302756; hg19: chr19-1272008; API