rs1045012

chr7-99386731-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.50

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]

ACMG classification

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	UniProt
ARPC1B	NM_005720.4	c.111G>C	p.Lys37Asn	missense_variant	3/10	ENST00000646101.2
ARPC1B	XM_024446628.2	c.111G>C	p.Lys37Asn	missense_variant	3/10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11563 AN: 152116 Hom.: 659 Cov.: 32

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

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.: 31 AF XY: 0.0444 AC XY: 32265 AN XY: 727160

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.: 32 AF XY: 0.0746 AC XY: 5554 AN XY: 74430

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

ARPC1B-related condition Benign:1

Benign, criteria provided, single submitter

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	23
Dann	Uncertain	1.0
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.91	D
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	T
MutationTaster	Benign	1.7e-18	P;P;P
PrimateAI	Uncertain	0.64	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	T
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

Other links and lift over

dbSNP: rs1045012; hg19: chr7-98984354; COSMIC: COSV53164397; COSMIC: COSV53164397;