Variant 3-113268444-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001378074.1(BOC):c.522A>C(p.Arg174Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000291 in 1,613,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

BOC
NM_001378074.1 missense, splice_region

Scores

Splicing: ADA: 0.09428

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

Variant links:

Genes affected

BOC (HGNC:17173): (BOC cell adhesion associated, oncogene regulated) The protein encoded by this gene is a member of the immunoglobulin/fibronectin type III repeat family. It is a component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells, and promotes myogenic differentiation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2014]

BOC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.1597842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BOC	NM_001378074.1 linkuse as main transcript	c.522A>C	p.Arg174Ser	missense_variant, splice_region_variant	5/20	ENST00000682979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BOC	ENST00000682979.1 linkuse as main transcript	c.522A>C	p.Arg174Ser	missense_variant, splice_region_variant	5/20		NM_001378074.1	A2	Q9BWV1-3

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000105

AC:

AN:

248144

Hom.:

AF XY:

0.0000819

AC XY:

AN XY:

134342

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000224

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000305

AC:

445

AN:

1461352

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

205

AN XY:

726928

show subpopulations

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:

0.000369

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000158

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000297

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.522A>C (p.R174S) alteration is located in exon 5 (coding exon 3) of the BOC gene. This alteration results from a A to C substitution at nucleotide position 522, causing the arginine (R) at amino acid position 174 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

0.39

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.18

T;.;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

N;N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.31

N;N;N

REVEL

Uncertain

0.38

Sift

Benign

0.39

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.12

B;B;B

Vest4

0.48

MutPred

0.52

Loss of MoRF binding (P = 0.0313);Loss of MoRF binding (P = 0.0313);Loss of MoRF binding (P = 0.0313);

MVP

0.70

MPC

0.42

ClinPred

0.046

GERP RS

2.0

Varity_R

0.19

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.094

dbscSNV1_RF

Benign

0.49

SpliceAI score (max)

0.060

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