Genetic Variant ARPC5:c.*531T>C (chr1-183627001-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005717.4(ARPC5):c.*531T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 153,550 control chromosomes in the GnomAD database, including 23,188 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 23073 hom., cov: 32)

Exomes 𝑓: 0.41 ( 115 hom. )

Consequence

ARPC5
NM_005717.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0260

Publications

14 publications found

Variant links:

Genes affected

ARPC5 (HGNC:708): (actin related protein 2/3 complex subunit 5) This gene encodes one of seven subunits of the human Arp2/3 protein complex. The Arp2/3 protein complex has been implicated in the control of actin polymerization in cells and has been conserved through evolution. The exact role of the protein encoded by this gene, the p16 subunit, has yet to be determined. Alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ARPC5 Gene-Disease associations (from GenCC):

immunodeficiency 113 with autoimmunity and autoinflammation
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ARPC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARPC5	NM_005717.4 link	c.*531T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000359856.11	NP_005708.1	O15511-1
ARPC5	NM_001270439.2 link	c.*531T>C		3_prime_UTR_variant	Exon 4 of 4		NP_001257368.1	O15511-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARPC5	ENST00000359856.11 link	c.*531T>C	3_prime_UTR_variant	Exon 4 of 4	1	NM_005717.4	ENSP00000352918.6	O15511-1
ARPC5	ENST00000294742.6 link	c.*531T>C	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000294742.6	O15511-2
ARPC5	ENST00000462965.1 link	n.1648T>C	non_coding_transcript_exon_variant	Exon 3 of 3	2
ARPC5	ENST00000367534.5 link	c.393+3460T>C	intron_variant	Intron 3 of 3	3		ENSP00000356504.1	B1ALC0

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80727

AN:

151964

Hom.:

23015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.459

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.456

Gnomad OTH

AF:

0.509

GnomAD4 exome

AF:

0.413

AC:

606

AN:

1468

Hom.:

115

Cov.:

AF XY:

0.410

AC XY:

353

AN XY:

860

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.396

AC:

AN:

164

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.100

AC:

AN:

South Asian (SAS)

AF:

0.284

AC:

AN:

116

European-Finnish (FIN)

AF:

0.450

AC:

179

AN:

398

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.421

AC:

308

AN:

732

Other (OTH)

AF:

0.413

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.532

AC:

80847

AN:

152082

Hom.:

23073

Cov.:

AF XY:

0.527

AC XY:

39173

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.747

AC:

30977

AN:

41496

American (AMR)

AF:

0.505

AC:

7713

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

1496

AN:

3470

East Asian (EAS)

AF:

0.245

AC:

1268

AN:

5182

South Asian (SAS)

AF:

0.400

AC:

1925

AN:

4818

European-Finnish (FIN)

AF:

0.459

AC:

4849

AN:

10554

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.456

AC:

31016

AN:

67962

Other (OTH)

AF:

0.514

AC:

1085

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1791

3582

5372

7163

8954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.485

Hom.:

51384

Bravo

AF:

0.547

Asia WGS

AF:

0.372

AC:

1296

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.5

(source)

DANN

Benign

0.66

PhyloP100

-0.026

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over