chr19-1231056-G-A

Variant summary

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

The NM_152769.3(CBARP):​c.1199C>T​(p.Pro400Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

CBARP
NM_152769.3 missense

Scores

3
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72
Variant links:
Genes affected
CBARP (HGNC:28617): (CACN subunit beta associated regulatory protein) Predicted to enable transmembrane transporter binding activity. Predicted to be involved in negative regulation of calcium ion-dependent exocytosis and negative regulation of voltage-gated calcium channel activity. Predicted to be located in synaptic vesicle membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Predicted to colocalize with growth cone and secretory granule. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.16217661).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CBARPNM_001393918.1 linkuse as main transcriptc.1154+45C>T intron_variant ENST00000650044.2 NP_001380847.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CBARPENST00000650044.2 linkuse as main transcriptc.1154+45C>T intron_variant NM_001393918.1 ENSP00000497208.1 Q8N350-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsMay 15, 2024The c.1199C>T (p.P400L) alteration is located in exon 9 (coding exon 8) of the CBARP gene. This alteration results from a C to T substitution at nucleotide position 1199, causing the proline (P) at amino acid position 400 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
BayesDel_addAF
Benign
-0.075
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
23
DANN
Uncertain
1.0
Eigen
Benign
-0.041
Eigen_PC
Benign
0.027
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.50
T
M_CAP
Uncertain
0.086
D
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-0.83
T
Sift4G
Uncertain
0.046
D
Vest4
0.29
MVP
0.58
MPC
0.48
ClinPred
0.97
D
GERP RS
3.4
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr19-1231055; API