2-202952595-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024744.17(CARF):​c.343C>A​(p.Leu115Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,614 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: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CARF
NM_024744.17 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51
Variant links:
Genes affected
CARF (HGNC:14435): (calcium responsive transcription factor) Enables DNA binding activity and DNA-binding transcription factor activity. Involved in cellular response to potassium ion and positive regulation of transcription from RNA polymerase II promoter in response to calcium ion. Predicted to be located in granular component. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
WDR12 (HGNC:14098): (WD repeat domain 12) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein is highly similar to the mouse WD repeat domain 12 protein at the amino acid level. The protein encoded by this gene is a component of a nucleolar protein complex that affects maturation of the large ribosomal subunit.[provided by RefSeq, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.23008311).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CARFNM_024744.17 linkc.343C>A p.Leu115Ile missense_variant Exon 6 of 17 ENST00000438828.4 NP_079020.13 Q8N187-1A0A024R405

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CARFENST00000438828.4 linkc.343C>A p.Leu115Ile missense_variant Exon 6 of 17 1 NM_024744.17 ENSP00000414644.1 Q8N187-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461614
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727120
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.343C>A (p.L115I) alteration is located in exon 6 (coding exon 3) of the CARF gene. This alteration results from a C to A substitution at nucleotide position 343, causing the leucine (L) at amino acid position 115 to be replaced by an isoleucine (I). 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
0.12
BayesDel_addAF
Benign
-0.052
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T;.;.;.;.;.;.;.;.;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.85
.;T;T;D;D;D;.;D;D;D
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.23
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.3
M;.;.;.;.;.;.;.;.;M
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.34
N;.;N;N;N;N;N;N;N;N
REVEL
Benign
0.094
Sift
Uncertain
0.023
D;.;D;D;D;D;T;D;D;D
Sift4G
Benign
0.093
T;T;D;T;D;T;T;D;D;T
Polyphen
0.99
D;.;.;D;.;.;.;.;.;D
Vest4
0.43
MutPred
0.25
Gain of sheet (P = 0.0221);.;.;Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);.;.;.;.;Gain of sheet (P = 0.0221);
MVP
0.34
MPC
0.77
ClinPred
0.90
D
GERP RS
3.6
Varity_R
0.075
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
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: chr2-203817318; API