Genetic Variant BCAN:p.Arg105Trp (chr1-156647022-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021948.5(BCAN):c.313C>T(p.Arg105Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,474 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R105G) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BCAN
NM_021948.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.278

Publications

0 publications found

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 links:

BCAN-AS2 (HGNC:56267): (BCAN antisense RNA 2)

BCAN-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAN	NM_021948.5 link	c.313C>T	p.Arg105Trp	missense_variant	Exon 3 of 14	ENST00000329117.10	NP_068767.3	Q96GW7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAN	ENST00000329117.10 link	c.313C>T	p.Arg105Trp	missense_variant	Exon 3 of 14	1	NM_021948.5	ENSP00000331210.4		Q96GW7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460474

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726460

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52920

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111396

Other (OTH)

AF:

0.00

AC:

AN:

60340

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

0.0037

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

.;D;T;.

Eigen

Benign

0.14

Eigen_PC

Benign

-0.022

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Pathogenic

0.35

MetaRNN

Uncertain

0.61

D;D;D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

2.9

.;M;.;M

PhyloP100

-0.28

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.7

D;D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0

.;D;.;D

Vest4

0.60, 0.63

MutPred

0.63

Loss of methylation at R105 (P = 0.0269);Loss of methylation at R105 (P = 0.0269);Loss of methylation at R105 (P = 0.0269);Loss of methylation at R105 (P = 0.0269);

MVP

0.82

MPC

1.7

ClinPred

0.99

GERP RS

2.5

Varity_R

0.50

gMVP

0.83

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over