chr1-156648066-C-T

Variant summary

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

The NM_021948.5(BCAN):​c.725C>T​(p.Pro242Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,932 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: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

BCAN
NM_021948.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15
Variant links:
Genes affected
BCAN (HGNC:23059): (brevican) This gene encodes a member of the lectican family of chondroitin sulfate proteoglycans that is specifically expressed in the central nervous system. This protein is developmentally regulated and may function in the formation of the brain extracellular matrix. This protein is highly expressed in gliomas and may promote the growth and cell motility of brain tumor cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]
BCAN-AS2 (HGNC:56267): (BCAN antisense RNA 2)

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=0.35444987).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCANNM_021948.5 linkc.725C>T p.Pro242Leu missense_variant Exon 5 of 14 ENST00000329117.10 NP_068767.3 Q96GW7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCANENST00000329117.10 linkc.725C>T p.Pro242Leu missense_variant Exon 5 of 14 1 NM_021948.5 ENSP00000331210.4 Q96GW7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251462
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135902
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461820
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
727212
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152112
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.725C>T (p.P242L) alteration is located in exon 5 (coding exon 4) of the BCAN gene. This alteration results from a C to T substitution at nucleotide position 725, causing the proline (P) at amino acid position 242 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
Benign
0.19
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.52
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;.;.
Eigen
Benign
0.13
Eigen_PC
Benign
0.037
FATHMM_MKL
Benign
0.38
N
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.35
T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
1.5
L;.;L
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-4.0
D;D;D
REVEL
Benign
0.10
Sift
Uncertain
0.0080
D;T;D
Sift4G
Uncertain
0.0050
D;T;D
Polyphen
1.0
D;.;D
Vest4
0.18
MVP
0.50
MPC
1.7
ClinPred
0.96
D
GERP RS
4.0
Varity_R
0.17
gMVP
0.82

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.

Other links and lift over

dbSNP: rs558655305; hg19: chr1-156617858; COSMIC: COSV61259752; COSMIC: COSV61259752; API