1-156648014-T-C

Variant names:

• chr1-156648014-T-C
• rs1679043026
• NM_021948.5:c.673T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021948.5(BCAN):​c.673T>C​(p.Tyr225His) variant causes a missense change. 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: 4.14

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 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	c.673T>C	p.Tyr225His	missense_variant	Exon 5 of 14	ENST00000329117.10	NP_068767.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAN	ENST00000329117.10	c.673T>C	p.Tyr225His	missense_variant	Exon 5 of 14	1	NM_021948.5	ENSP00000331210.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.673T>C (p.Y225H) alteration is located in exon 5 (coding exon 4) of the BCAN gene. This alteration results from a T to C substitution at nucleotide position 673, causing the tyrosine (Y) at amino acid position 225 to be replaced by a histidine (H). 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	0.81
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.82	T;D;T
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.;M
PrimateAI	Pathogenic	0.80	D
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;T;D
Sift4G	Uncertain	0.046	D;T;D
Polyphen		1.0	D;.;P
Vest4		0.52
MutPred		0.63		Loss of phosphorylation at Y225 (P = 0.0113);.;Loss of phosphorylation at Y225 (P = 0.0113);
MVP		0.42
MPC		1.8
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.52
gMVP		0.88

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

Other links and lift over

dbSNP: rs1679043026; hg19: chr1-156617806;