rs1045012

Positions:

chr7-99386731-G-C

Variant summary

Our verdict is Benign. Variant got -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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ARPC1B	NM_005720.4 linkuse as main transcript	c.111G>C	p.Lys37Asn	missense_variant	3/10	ENST00000646101.2	NP_005711.1
ARPC1B	XM_024446628.2 linkuse as main transcript	c.111G>C	p.Lys37Asn	missense_variant	3/10		XP_024302396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC1B	ENST00000646101.2 linkuse as main transcript	c.111G>C	p.Lys37Asn	missense_variant	3/10		NM_005720.4	ENSP00000496599	P1

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

GnomAD3 exomes

AF:

0.0557

AC:

13989

AN:

251054

Hom.:

547

AF XY:

0.0519

AC XY:

7041

AN XY:

135694

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 SAS exome

AF:

0.0408

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

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.0814

Gnomad4 ASJ exome

AF:

0.0382

Gnomad4 EAS exome

AF:

0.0224

Gnomad4 SAS exome

AF:

0.0411

Gnomad4 FIN exome

AF:

0.0645

Gnomad4 NFE exome

AF:

0.0404

Gnomad4 OTH exome

AF:

0.0479

GnomAD4 genome

AF:

0.0760

AC:

11575

AN:

152234

Hom.:

658

Cov.:

AF XY:

0.0746

AC XY:

5554

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.0570

Gnomad4 ASJ

AF:

0.0410

Gnomad4 EAS

AF:

0.0263

Gnomad4 SAS

AF:

0.0476

Gnomad4 FIN

AF:

0.0611

Gnomad4 NFE

AF:

0.0407

Gnomad4 OTH

AF:

0.0558

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

ARPC1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 2019

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

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

MutationTaster

Benign

1.7e-18

P;P;P

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

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

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