Variant 19-1271453-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001300829.2(CIRBP):c.335G>T(p.Arg112Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,457,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CIRBP
NM_001300829.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.26

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]

CIRBP links:

CIRBP (HGNC:):

CIRBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35030907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIRBP	NM_001300829.2 linkuse as main transcript	c.335G>T	p.Arg112Leu	missense_variant	4/6	ENST00000587896.6	NP_001287758.1	Q14011D6W5Y5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIRBP	ENST00000587896.6 linkuse as main transcript	c.335G>T	p.Arg112Leu	missense_variant	4/6	2	NM_001300829.2	ENSP00000466025.1		D6W5Y5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245344

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132762

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:

0.00000904

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1457506

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724862

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:

0.0000243

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Dec 14, 2023

The c.335G>T (p.R112L) alteration is located in exon 4 (coding exon 3) of the CIRBP gene. This alteration results from a G to T substitution at nucleotide position 335, causing the arginine (R) at amino acid position 112 to be replaced by a leucine (L). 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

0.50

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;T;T;.;T;T;T;T;.;T;.;T;T;T;.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.0083

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;.;.;.;D;.;.;D;.;.;D;.;.;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.35

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.8

L;L;L;.;.;L;.;.;.;.;.;.;.;L;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.8

.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.

REVEL

Uncertain

0.34

Sift

Benign

0.42

.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.

Sift4G

Benign

0.12

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0

B;B;B;.;.;B;P;P;.;P;.;P;P;B;.;.

Vest4

0.61

MutPred

0.51

Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);Loss of methylation at R112 (P = 0.002);

MVP

0.76

MPC

0.81

ClinPred

0.73

GERP RS

2.4

Varity_R

0.14

gMVP

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over