chr1-156647099-C-A

Position:

• chr1-156647099-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_021948.5(BCAN):​c.390C>A​(p.Asn130Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCAN NM_021948.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.297

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity PGCB_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCAN	NM_021948.5	c.390C>A	p.Asn130Lys	missense_variant	3/14	ENST00000329117.10	NP_068767.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCAN	ENST00000329117.10	c.390C>A	p.Asn130Lys	missense_variant	3/14	1	NM_021948.5	ENSP00000331210.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.390C>A (p.N130K) alteration is located in exon 3 (coding exon 2) of the BCAN gene. This alteration results from a C to A substitution at nucleotide position 390, causing the asparagine (N) at amino acid position 130 to be replaced by a lysine (K). 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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	.;D;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;D;D;T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	.;L;.;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.0	D;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D;T;T;D
Sift4G	Uncertain	0.010	D;D;T;T
Polyphen		1.0, 0.74	.;D;.;P
Vest4		0.65, 0.64
MutPred		0.54		Gain of ubiquitination at N130 (P = 0.0101);Gain of ubiquitination at N130 (P = 0.0101);Gain of ubiquitination at N130 (P = 0.0101);Gain of ubiquitination at N130 (P = 0.0101);
MVP		0.34
MPC		1.6
ClinPred		0.99	D
GERP RS		0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-156616891;