chr1-156647119-G-T

Position:

• chr1-156647119-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_021948.5(BCAN):​c.410G>T​(p.Cys137Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 9.88

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCAN	NM_021948.5	c.410G>T	p.Cys137Phe	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.410G>T	p.Cys137Phe	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

Jan 05, 2022

The c.410G>T (p.C137F) alteration is located in exon 3 (coding exon 2) of the BCAN gene. This alteration results from a G to T substitution at nucleotide position 410, causing the cysteine (C) at amino acid position 137 to be replaced by a phenylalanine (F). 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	1.0
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	34
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.84	.;D;T;.;.
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.6	.;H;.;.;H
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-11	D;D;D;D;D
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;T;D
Polyphen		1.0	.;D;.;.;D
Vest4		0.95, 0.94
MutPred		0.93		Loss of catalytic residue at V139 (P = 0.0874);Loss of catalytic residue at V139 (P = 0.0874);Loss of catalytic residue at V139 (P = 0.0874);.;Loss of catalytic residue at V139 (P = 0.0874);
MVP		0.64
MPC		2.1
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.97
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr1-156616911;