chr1-156646806-C-A

Variant names:

• chr1-156646806-C-A
• rs1027264628
• NM_021948.5:c.97C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021948.5(BCAN):​c.97C>A​(p.Arg33Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,408,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: BCAN NM_021948.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12355253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAN	NM_021948.5	c.97C>A	p.Arg33Ser	missense_variant	Exon 3 of 14	ENST00000329117.10	NP_068767.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAN	ENST00000329117.10	c.97C>A	p.Arg33Ser	missense_variant	Exon 3 of 14	1	NM_021948.5	ENSP00000331210.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408620 Hom.: 0 Cov.: 33 AF XY: 0.00000144 AC XY: 1 AN XY: 695058

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.21e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.97C>A (p.R33S) 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 97, causing the arginine (R) at amino acid position 33 to be replaced by a serine (S). 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.045	.;T;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.10	.;N;.;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.21	N;N;N;N
REVEL	Benign	0.052
Sift	Benign	0.29	T;T;T;T
Sift4G	Uncertain	0.015	D;T;D;T
Polyphen		0.53, 0.14	.;P;.;B
Vest4		0.34, 0.35
MutPred		0.31		Gain of phosphorylation at R33 (P = 0.0465);Gain of phosphorylation at R33 (P = 0.0465);Gain of phosphorylation at R33 (P = 0.0465);Gain of phosphorylation at R33 (P = 0.0465);
MVP		0.34
MPC		1.6
ClinPred		0.83	D
GERP RS		3.4
Varity_R		0.14
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1027264628; hg19: chr1-156616598;