Genetic Variant ARPC1A:c.983+519C>T (chr7-99360257-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006409.4(ARPC1A):c.983+519C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 162,694 control chromosomes in the GnomAD database, including 737 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 0.083 ( 719 hom., cov: 31)

Exomes 𝑓: 0.050 ( 18 hom. )

Consequence

ARPC1A
NM_006409.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

Publications

25 publications found

Variant links:

Genes affected

ARPC1A (HGNC:703): (actin related protein 2/3 complex subunit 1A) 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 ARPC1B. 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ARPC1A links:

ENSG00000284292 (HGNC:):

ENSG00000284292 links:

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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 = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARPC1A	NM_006409.4 link	c.983+519C>T		intron_variant	Intron 8 of 9	ENST00000262942.10	NP_006400.2	Q92747-1V9HVZ6
ARPC1A	NM_001190996.2 link	c.941+519C>T		intron_variant	Intron 8 of 9		NP_001177925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARPC1A	ENST00000262942.10 link	c.983+519C>T		intron_variant	Intron 8 of 9	1	NM_006409.4	ENSP00000262942.5		Q92747-1
ENSG00000284292	ENST00000638617.1 link	c.983+519C>T		intron_variant	Intron 8 of 16	5		ENSP00000491073.1		A0A1W2PNV4

Frequencies

GnomAD3 genomes

AF:

0.0829

AC:

12570

AN:

151678

Hom.:

715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0678

Gnomad ASJ

AF:

0.0537

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.0789

Gnomad FIN

AF:

0.0661

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0463

Gnomad OTH

AF:

0.0761

GnomAD4 exome

AF:

0.0501

AC:

547

AN:

10922

Hom.:

Cov.:

AF XY:

0.0541

AC XY:

307

AN XY:

5678

show subpopulations

African (AFR)

AF:

0.170

AC:

AN:

194

American (AMR)

AF:

0.0507

AC:

115

AN:

2268

Ashkenazi Jewish (ASJ)

AF:

0.0615

AC:

AN:

130

East Asian (EAS)

AF:

0.00326

AC:

AN:

614

South Asian (SAS)

AF:

0.0807

AC:

106

AN:

1314

European-Finnish (FIN)

AF:

0.0571

AC:

AN:

140

Middle Eastern (MID)

AF:

0.0625

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0439

AC:

252

AN:

5746

Other (OTH)

AF:

0.0440

AC:

AN:

500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0830

AC:

12597

AN:

151772

Hom.:

719

Cov.:

AF XY:

0.0841

AC XY:

6235

AN XY:

74138

show subpopulations

African (AFR)

AF:

0.167

AC:

6897

AN:

41340

American (AMR)

AF:

0.0677

AC:

1031

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.0537

AC:

186

AN:

3464

East Asian (EAS)

AF:

0.00348

AC:

AN:

5176

South Asian (SAS)

AF:

0.0795

AC:

381

AN:

4792

European-Finnish (FIN)

AF:

0.0661

AC:

693

AN:

10490

Middle Eastern (MID)

AF:

0.0342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0463

AC:

3144

AN:

67966

Other (OTH)

AF:

0.0821

AC:

173

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

559

1118

1676

2235

2794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0560

Hom.:

1079

Bravo

AF:

0.0857

Asia WGS

AF:

0.0420

AC:

147

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

1.8

(source)

DANN

Benign

0.36

PhyloP100

-0.13

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

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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