1-156648066-C-A

Variant names:

• chr1-156648066-C-A
• rs558655305
• NM_021948.5:c.725C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021948.5(BCAN):​c.725C>A​(p.Pro242Gln) 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. 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. P242L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCAN NM_021948.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38160238).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021948.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAN	NM_021948.5	MANE Select	c.725C>A	p.Pro242Gln	missense	Exon 5 of 14	NP_068767.3
	BCAN	NM_198427.2		c.725C>A	p.Pro242Gln	missense	Exon 5 of 8	NP_940819.1	Q96GW7-2
	BCAN-AS2	NR_182279.1		n.127-912G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAN	ENST00000329117.10	TSL:1 MANE Select	c.725C>A	p.Pro242Gln	missense	Exon 5 of 14	ENSP00000331210.4	Q96GW7-1
	BCAN	ENST00000361588.5	TSL:1	c.725C>A	p.Pro242Gln	missense	Exon 5 of 8	ENSP00000354925.5	Q96GW7-2
	BCAN	ENST00000884916.1		c.758C>A	p.Pro253Gln	missense	Exon 5 of 14	ENSP00000554975.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.069
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.52
MutPred		0.63		Gain of catalytic residue at P242 (P = 0.0558)
MVP		0.50
MPC		1.6
ClinPred		0.95	D
GERP RS		4.0
Varity_R		0.17
gMVP		0.78
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs558655305; hg19: chr1-156617858;