1-156647022-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.278

Variant links:

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 links:

BCAN-AS2 (HGNC:56267): (BCAN antisense RNA 2)

BCAN-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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. gnomad4_exome 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 gnomad4_exome. There are 10620 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAN	NM_021948.5 link	c.313C>G	p.Arg105Gly	missense_variant	Exon 3 of 14	ENST00000329117.10	NP_068767.3	Q96GW7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAN	ENST00000329117.10 link	c.313C>G	p.Arg105Gly	missense_variant	Exon 3 of 14	1	NM_021948.5	ENSP00000331210.4		Q96GW7-1

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2220

AN:

152204

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0177

AC:

4380

AN:

248134

Hom.:

AF XY:

0.0172

AC XY:

2320

AN XY:

134720

show subpopulations

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 SAS exome

AF:

0.0102

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.:

AF XY:

0.0146

AC XY:

10620

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.0172

Gnomad4 ASJ exome

AF:

0.00997

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.0681

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.0138

GnomAD4 genome

AF:

0.0146

AC:

2221

AN:

152322

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1271

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.0753

Gnomad4 NFE

AF:

0.0152

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0138

Hom.:

Bravo

AF:

0.00926

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0135

AC:

116

ExAC

AF:

0.0164

AC:

1988

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0125

EpiControl

AF:

0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

.;D;T;.

Eigen

Benign

-0.064

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.85

D;T;D;T

MetaRNN

Benign

0.0029

T;T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.7

.;L;.;L

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-4.3

D;D;D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0060

D;D;D;T

Sift4G

Uncertain

0.023

D;T;T;D

Polyphen

0.99, 0.86

.;D;.;P

Vest4

0.24, 0.43

MPC

1.9

ClinPred

0.022

GERP RS

2.5

Varity_R

0.39

gMVP

0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over