rs372607625

Variant summary

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

The NM_016366.3(CABP2):​c.520G>C​(p.Val174Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V174M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

CABP2
NM_016366.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.01
Variant links:
Genes affected
CABP2 (HGNC:1385): (calcium binding protein 2) This gene belongs to a subfamily of calcium binding proteins that share similarity to calmodulin. Like calmodulin, these family members can likely stimulate calmodulin-dependent kinase II and the protein phosphatase calcineurin. Calcium binding proteins are an important component of calcium mediated cellular signal transduction. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

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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=0.08896893).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CABP2NM_016366.3 linkc.520G>C p.Val174Leu missense_variant Exon 6 of 7 ENST00000294288.5 NP_057450.2 Q9NPB3-1
CABP2NM_001318496.2 linkc.538G>C p.Val180Leu missense_variant Exon 6 of 7 NP_001305425.1 Q9NPB3F1T0K2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CABP2ENST00000294288.5 linkc.520G>C p.Val174Leu missense_variant Exon 6 of 7 1 NM_016366.3 ENSP00000294288.4 Q9NPB3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458764
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
725780
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.023
DANN
Benign
0.86
DEOGEN2
Benign
0.048
.;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.036
N
LIST_S2
Benign
0.81
T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.089
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.85
.;L;.
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.28
N;N;.
REVEL
Benign
0.081
Sift
Benign
0.27
T;T;.
Sift4G
Benign
0.36
T;T;.
Polyphen
0.0
B;B;.
Vest4
0.12
MutPred
0.48
.;Gain of disorder (P = 0.1181);.;
MVP
0.51
MPC
0.27
ClinPred
0.10
T
GERP RS
-3.2
Varity_R
0.042
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr11-67287381; API