NM_001378074.1:c.522A>C

Variant names:

• chr3-113268444-A-C
• rs144251369
• NM_001378074.1:c.522A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 14/24 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 (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• 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
• Publications: 2 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]

LOC124909409 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1597842).

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.522A>C	p.Arg174Ser	missense splice_region	Exon 5 of 20	NP_001365003.1	Q9BWV1-3
	BOC	NM_001301861.2		c.522A>C	p.Arg174Ser	missense splice_region	Exon 5 of 20	NP_001288790.1	Q9BWV1-3
	BOC	NM_001378073.1		c.522A>C	p.Arg174Ser	missense splice_region	Exon 5 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.522A>C	p.Arg174Ser	missense splice_region	Exon 5 of 20	ENSP00000507783.1	Q9BWV1-3
	BOC	ENST00000273395.8	TSL:1	c.522A>C	p.Arg174Ser	missense splice_region	Exon 5 of 20	ENSP00000273395.4	Q9BWV1-3
	BOC	ENST00000495514.5	TSL:1	c.522A>C	p.Arg174Ser	missense splice_region	Exon 5 of 20	ENSP00000418663.1	Q9BWV1-1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152194 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000105 AC: 26 AN: 248144 AF XY: 0.0000819

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 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.: 0 Cov.: 31 AF XY: 0.000282 AC XY: 205 AN XY: 726928

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

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000369 AC: 410 AN: 1111836

Other (OTH) AF: 0.000580 AC: 35 AN: 60346

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74346

African (AFR) AF: 0.0000724 AC: 3 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68026

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000229 Hom.: 0

Bravo AF: 0.000208

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000164

EpiControl AF: 0.000297

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	Uncertain	0.39
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	N
PhyloP100		4.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.31	N
REVEL	Uncertain	0.38
Sift	Benign	0.39	T
Sift4G	Benign	0.26	T
Polyphen		0.12	B
Vest4		0.48
MutPred		0.52		Loss of MoRF binding (P = 0.0313)
MVP		0.70
MPC		0.42
ClinPred		0.046	T
GERP RS		2.0
Varity_R		0.19
gMVP		0.66
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs144251369; hg19: chr3-112987291;