1-156651462-C-T

Variant names:

• chr1-156651462-C-T
• NM_021948.5:c.1070C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021948.5(BCAN):​c.1070C>T​(p.Ala357Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A357T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BCAN NM_021948.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.211
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07356486).

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.1070C>T	p.Ala357Val	missense	Exon 7 of 14	NP_068767.3
	BCAN	NM_198427.2		c.1070C>T	p.Ala357Val	missense	Exon 7 of 8	NP_940819.1	Q96GW7-2
	BCAN-AS2	NR_182279.1		n.127-4308G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAN	ENST00000329117.10	TSL:1 MANE Select	c.1070C>T	p.Ala357Val	missense	Exon 7 of 14	ENSP00000331210.4	Q96GW7-1
	BCAN	ENST00000361588.5	TSL:1	c.1070C>T	p.Ala357Val	missense	Exon 7 of 8	ENSP00000354925.5	Q96GW7-2
	BCAN	ENST00000884916.1		c.1103C>T	p.Ala368Val	missense	Exon 7 of 14	ENSP00000554975.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461116 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726848

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111766

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.1
DANN	Benign	0.87
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.21
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.023
Sift	Benign	0.28	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.066
MutPred		0.22		Loss of disorder (P = 0.0644)
MVP		0.22
MPC		0.099
ClinPred		0.042	T
GERP RS		-2.8
Varity_R		0.026
gMVP		0.36
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr1-156621254;