chr3-113250710-C-T

Variant summary

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

The NM_001378074.1(BOC):​c.253C>T​(p.Leu85Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BOC
NM_001378074.1 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87
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]

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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=0.15182123).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BOCNM_001378074.1 linkc.253C>T p.Leu85Phe missense_variant Exon 4 of 20 ENST00000682979.1 NP_001365003.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BOCENST00000682979.1 linkc.253C>T p.Leu85Phe missense_variant Exon 4 of 20 NM_001378074.1 ENSP00000507783.1 Q9BWV1-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251452
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.253C>T (p.L85F) alteration is located in exon 4 (coding exon 2) of the BOC gene. This alteration results from a C to T substitution at nucleotide position 253, causing the leucine (L) at amino acid position 85 to be replaced by a phenylalanine (F). 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
Benign
0.15
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
T;T;.;T;T
Eigen
Benign
0.032
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.68
.;.;T;T;T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.15
T;T;T;T;T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
1.8
L;.;L;L;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.76
N;N;N;N;N
REVEL
Benign
0.071
Sift
Benign
0.26
T;T;T;T;T
Sift4G
Benign
0.66
T;T;T;T;T
Polyphen
0.0030
B;B;B;B;B
Vest4
0.17
MutPred
0.52
Gain of catalytic residue at L85 (P = 0.0657);Gain of catalytic residue at L85 (P = 0.0657);Gain of catalytic residue at L85 (P = 0.0657);Gain of catalytic residue at L85 (P = 0.0657);Gain of catalytic residue at L85 (P = 0.0657);
MVP
0.81
MPC
0.26
ClinPred
0.25
T
GERP RS
4.9
Varity_R
0.074
gMVP
0.46

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.

Other links and lift over

dbSNP: rs1192028182; hg19: chr3-112969557; API