chr3-113250813-C-T

Variant names:

• chr3-113250813-C-T
• NM_001378074.1:c.356C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001378074.1(BOC):​c.356C>T​(p.Pro119Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BOC NM_001378074.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3282363).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378074.1. 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
	BOC	NM_001378074.1	MANE Select	c.356C>T	p.Pro119Leu	missense	Exon 4 of 20	NP_001365003.1	Q9BWV1-3
	BOC	NM_001301861.2		c.356C>T	p.Pro119Leu	missense	Exon 4 of 20	NP_001288790.1	Q9BWV1-3
	BOC	NM_001378073.1		c.356C>T	p.Pro119Leu	missense	Exon 4 of 20	NP_001365002.1	Q9BWV1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOC	ENST00000682979.1	MANE Select	c.356C>T	p.Pro119Leu	missense	Exon 4 of 20	ENSP00000507783.1	Q9BWV1-3
	BOC	ENST00000273395.8	TSL:1	c.356C>T	p.Pro119Leu	missense	Exon 4 of 20	ENSP00000273395.4	Q9BWV1-3
	BOC	ENST00000495514.5	TSL:1	c.356C>T	p.Pro119Leu	missense	Exon 4 of 20	ENSP00000418663.1	Q9BWV1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461388 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727020

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.0000166 AC: 1 AN: 60358

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.84	D
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.32
Sift	Benign	0.075	T
Sift4G	Benign	0.15	T
Polyphen		0.097	B
Vest4		0.49
MutPred		0.55		Loss of sheet (P = 0.0457)
MVP		0.71
MPC		0.27
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.76
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr3-112969660;