chr1-156651473-G-A

Position:

• chr1-156651473-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021948.5(BCAN):​c.1081G>A​(p.Ala361Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. 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: 0.550

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0612081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCAN	NM_021948.5	c.1081G>A	p.Ala361Thr	missense_variant	7/14	ENST00000329117.10	NP_068767.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCAN	ENST00000329117.10	c.1081G>A	p.Ala361Thr	missense_variant	7/14	1	NM_021948.5	ENSP00000331210.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Sep 23, 2023

The c.1081G>A (p.A361T) alteration is located in exon 7 (coding exon 6) of the BCAN gene. This alteration results from a G to A substitution at nucleotide position 1081, causing the alanine (A) at amino acid position 361 to be replaced by a threonine (T). 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	0.066
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.76
DEOGEN2	Benign	0.066	T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.010	N;N
REVEL	Benign	0.027
Sift	Benign	0.69	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.040	B;B
Vest4		0.057
MutPred		0.14		Gain of glycosylation at A361 (P = 0.0287);Gain of glycosylation at A361 (P = 0.0287);
MVP		0.31
MPC		0.095
ClinPred		0.14	T
GERP RS		3.3
Varity_R		0.023
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156621265; COSMIC: COSV100228516; COSMIC: COSV100228516;