1-156647022-C-G

Variant names:

• chr1-156647022-C-G
• rs115373136
• NM_021948.5:c.313C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_021948.5(BCAN):​c.313C>G​(p.Arg105Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,612,772 control chromosomes in the GnomAD database, including 309 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (39 hom., cov: 32)
  • Exomes 𝑓: 0.015 (270 hom.)
• Consequence: BCAN NM_021948.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.278
• Publications: 9 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029218197).
• BP6: Variant 1-156647022-C-G is Benign according to our data. Variant chr1-156647022-C-G is described in ClinVar as Benign. ClinVar VariationId is 402409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0148 (21607/1460450) while in subpopulation AMR AF = 0.0172 (770/44654). AF 95% confidence interval is 0.0162. There are 270 homozygotes in GnomAdExome4. There are 10620 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

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.313C>G	p.Arg105Gly	missense	Exon 3 of 14	NP_068767.3
	BCAN	NM_198427.2		c.313C>G	p.Arg105Gly	missense	Exon 3 of 8	NP_940819.1
	BCAN-AS2	NR_182279.1		n.259G>C		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAN	ENST00000329117.10	TSL:1 MANE Select	c.313C>G	p.Arg105Gly	missense	Exon 3 of 14	ENSP00000331210.4
	BCAN	ENST00000361588.5	TSL:1	c.313C>G	p.Arg105Gly	missense	Exon 3 of 8	ENSP00000354925.5
	BCAN	ENST00000884916.1		c.346C>G	p.Arg116Gly	missense	Exon 3 of 14	ENSP00000554975.1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2220 AN: 152204 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.0177 AC: 4380 AN: 248134 AF XY: 0.0172

Gnomad AFR exome AF: 0.00201

Gnomad AMR exome AF: 0.0176

Gnomad ASJ exome AF: 0.00983

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0708

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.0160

GnomAD4 exome AF: 0.0148 AC: 21607 AN: 1460450 Hom.: 270 Cov.: 34 AF XY: 0.0146 AC XY: 10620 AN XY: 726438

African (AFR) AF: 0.00191 AC: 64 AN: 33466

American (AMR) AF: 0.0172 AC: 770 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00997 AC: 260 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0108 AC: 930 AN: 86184

European-Finnish (FIN) AF: 0.0681 AC: 3606 AN: 52920

Middle Eastern (MID) AF: 0.00382 AC: 22 AN: 5764

European-Non Finnish (NFE) AF: 0.0136 AC: 15120 AN: 1111374

Other (OTH) AF: 0.0138 AC: 835 AN: 60340

GnomAD4 genome AF: 0.0146 AC: 2221 AN: 152322 Hom.: 39 Cov.: 32 AF XY: 0.0171 AC XY: 1271 AN XY: 74476

African (AFR) AF: 0.00231 AC: 96 AN: 41580

American (AMR) AF: 0.0114 AC: 175 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4828

European-Finnish (FIN) AF: 0.0753 AC: 799 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0152 AC: 1031 AN: 68018

Other (OTH) AF: 0.0147 AC: 31 AN: 2116

Alfa AF: 0.0138 Hom.: 19

Bravo AF: 0.00926

TwinsUK AF: 0.0116 AC: 43

ALSPAC AF: 0.0114 AC: 44

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.0135 AC: 116

ExAC AF: 0.0164 AC: 1988

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0125

EpiControl AF: 0.0132

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.28
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.29
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.023	D
Polyphen		0.99	D
Vest4		0.24
MPC		1.9
ClinPred		0.022	T
GERP RS		2.5
Varity_R		0.39
gMVP		0.78
Mutation Taster		=90/10	polymorphism (auto)

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

dbSNP: rs115373136; hg19: chr1-156616814; COSMIC: COSV107336695; COSMIC: COSV107336695;