1-156647022-C-G

Position:

• chr1-156647022-C-G

Variant summary

Our verdict is Benign. Variant got -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. 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

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 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/exons	MANE	UniProt
BCAN	NM_021948.5	c.313C>G	p.Arg105Gly	missense_variant	3/14	ENST00000329117.10
BCAN-AS2	NR_182279.1	n.259G>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAN	ENST00000329117.10	c.313C>G	p.Arg105Gly	missense_variant	3/14	1	NM_021948.5	P1
BCAN-AS2	ENST00000448869.1	n.243G>C		non_coding_transcript_exon_variant	2/2	2

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

GnomAD3 exomes AF: 0.0177 AC: 4380 AN: 248134 Hom.: 72 AF XY: 0.0172 AC XY: 2320 AN XY: 134720

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.: 34 AF XY: 0.0146 AC XY: 10620 AN XY: 726438

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.: 39 Cov.: 32 AF XY: 0.0171 AC XY: 1271 AN XY: 74476

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.: 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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.85	D;T;D;T
MetaRNN	Benign	0.0029	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.7	.;L;.;L
MutationTaster	Benign	0.87	D;D
PrimateAI	Uncertain	0.63	T
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	T
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

Other links and lift over

dbSNP: rs115373136; hg19: chr1-156616814;