Variant chr19-1271465-G-A 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.347G>A(p.Arg116Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000412 in 1,455,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CIRBP
NM_001300829.2 missense, splice_region

Scores

Splicing: ADA: 0.3212

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

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:

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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=0.42092562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIRBP	NM_001300829.2 linkuse as main transcript	c.347G>A	p.Arg116Lys	missense_variant, splice_region_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.347G>A	p.Arg116Lys	missense_variant, splice_region_variant	4/6	2	NM_001300829.2	ENSP00000466025.1		D6W5Y5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455418

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723582

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:

0.00000541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 20, 2023

The c.347G>A (p.R116K) alteration is located in exon 4 (coding exon 3) of the CIRBP gene. This alteration results from a G to A substitution at nucleotide position 347, causing the arginine (R) at amino acid position 116 to be replaced by a lysine (K). 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

Benign

0.25

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

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

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

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

M_CAP

Benign

0.074

MetaRNN

Benign

0.42

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

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.3

M;M;M;.;.;M;.;.;.;.;.;.;.;M;.;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.3

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

REVEL

Benign

0.24

Sift

Uncertain

0.025

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

Sift4G

Benign

0.72

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

Polyphen

0.88

P;P;P;.;.;P;D;D;.;D;.;D;D;P;.;.

Vest4

0.53

MutPred

0.44

Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);Gain of solvent accessibility (P = 0.0059);

MVP

0.76

MPC

0.66

ClinPred

0.93

GERP RS

3.7

Varity_R

0.31

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.32

dbscSNV1_RF

Benign

0.66

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