rs1045012

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005720.4(ARPC1B):c.111G>C(p.Lys37Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 1,613,932 control chromosomes in the GnomAD database, including 2,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 658 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1900 hom. )

Consequence

ARPC1B
NM_005720.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.50

Publications

24 publications found

Variant links:

Genes affected

ARPC1B (HGNC:704): (actin related protein 2/3 complex subunit 1B) This gene encodes one of seven subunits of the human Arp2/3 protein complex. This subunit is a member of the SOP2 family of proteins and is most similar to the protein encoded by gene ARPC1A. The similarity between these two proteins suggests that they both may function as p41 subunit of the human Arp2/3 complex that has been implicated in the control of actin polymerization in cells. It is possible that the p41 subunit is involved in assembling and maintaining the structure of the Arp2/3 complex. Multiple versions of the p41 subunit may adapt the functions of the complex to different cell types or developmental stages. This protein also has a role in centrosomal homeostasis by being an activator and substrate of the Aurora A kinase. [provided by RefSeq, Mar 2011]

ARPC1B Gene-Disease associations (from GenCC):

platelet abnormalities with eosinophilia and immune-mediated inflammatory disease
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ARPC1B links:

ENSG00000284292 (HGNC:):

ENSG00000284292 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017987788).

BP6

Variant 7-99386731-G-C is Benign according to our data. Variant chr7-99386731-G-C is described in ClinVar as [Benign]. Clinvar id is 1170233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARPC1B	NM_005720.4 link	c.111G>C	p.Lys37Asn	missense_variant	Exon 3 of 10	ENST00000646101.2	NP_005711.1	O15143A4D275
ARPC1B	XM_024446628.2 link	c.111G>C	p.Lys37Asn	missense_variant	Exon 3 of 10		XP_024302396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARPC1B	ENST00000646101.2 link	c.111G>C	p.Lys37Asn	missense_variant	Exon 3 of 10		NM_005720.4	ENSP00000496599.1		O15143
ENSG00000284292	ENST00000638617.1 link	c.1107G>C	p.Lys369Asn	missense_variant	Exon 10 of 17	5		ENSP00000491073.1		A0A1W2PNV4

Frequencies

GnomAD3 genomes

AF:

0.0760

AC:

11563

AN:

152116

Hom.:

659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0569

Gnomad ASJ

AF:

0.0410

Gnomad EAS

AF:

0.0262

Gnomad SAS

AF:

0.0471

Gnomad FIN

AF:

0.0611

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0408

Gnomad OTH

AF:

0.0569

GnomAD2 exomes

AF:

0.0557

AC:

13989

AN:

251054

AF XY:

0.0519

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.0856

Gnomad ASJ exome

AF:

0.0355

Gnomad EAS exome

AF:

0.0296

Gnomad FIN exome

AF:

0.0633

Gnomad NFE exome

AF:

0.0413

Gnomad OTH exome

AF:

0.0460

GnomAD4 exome

AF:

0.0451

AC:

65989

AN:

1461698

Hom.:

1900

Cov.:

AF XY:

0.0444

AC XY:

32265

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.165

AC:

5525

AN:

33466

American (AMR)

AF:

0.0814

AC:

3638

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0382

AC:

998

AN:

26132

East Asian (EAS)

AF:

0.0224

AC:

888

AN:

39698

South Asian (SAS)

AF:

0.0411

AC:

3549

AN:

86254

European-Finnish (FIN)

AF:

0.0645

AC:

3443

AN:

53392

Middle Eastern (MID)

AF:

0.0262

AC:

151

AN:

5766

European-Non Finnish (NFE)

AF:

0.0404

AC:

44903

AN:

1111880

Other (OTH)

AF:

0.0479

AC:

2894

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

3184

6368

9551

12735

15919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0760

AC:

11575

AN:

152234

Hom.:

658

Cov.:

AF XY:

0.0746

AC XY:

5554

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.159

AC:

6599

AN:

41528

American (AMR)

AF:

0.0570

AC:

871

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0410

AC:

142

AN:

3466

East Asian (EAS)

AF:

0.0263

AC:

136

AN:

5178

South Asian (SAS)

AF:

0.0476

AC:

229

AN:

4814

European-Finnish (FIN)

AF:

0.0611

AC:

649

AN:

10618

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0407

AC:

2771

AN:

68016

Other (OTH)

AF:

0.0558

AC:

118

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

525

1050

1575

2100

2625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0447

Hom.:

132

Bravo

AF:

0.0812

TwinsUK

AF:

0.0399

AC:

148

ALSPAC

AF:

0.0454

AC:

175

ESP6500AA

AF:

0.156

AC:

688

ESP6500EA

AF:

0.0417

AC:

359

ExAC

AF:

0.0579

AC:

7030

Asia WGS

AF:

0.0510

AC:

177

AN:

3478

EpiCase

AF:

0.0348

EpiControl

AF:

0.0381

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

ARPC1B-related disorder

Benign:1

May 08, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

.;T;.;T;T;T;.;.;T;T;T;T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

D;D;D;.;.;.;D;D;.;.;.;.;D

MetaRNN

Benign

0.0018

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.8

.;.;.;M;M;M;.;.;M;M;M;M;M

PhyloP100

1.5

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.2

.;D;D;.;D;D;D;D;D;D;D;D;.

REVEL

Benign

0.25

Sift

Benign

0.22

.;T;T;.;D;T;T;T;T;T;D;T;.

Sift4G

Benign

0.31

.;T;T;.;T;T;T;T;T;T;T;T;.

Polyphen

0.99

.;.;.;D;D;D;.;.;D;D;D;D;D

Vest4

0.22, 0.22

MutPred

0.14

.;Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);Loss of ubiquitination at K37 (P = 0.0183);

MPC

0.82

ClinPred

0.029

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.67

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs1045012

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over