rs740160

Positions:

• chr7-99360257-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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]

ENSG00000284292 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ARPC1A	NM_006409.4	c.983+519C>T		intron_variant		ENST00000262942.10	NP_006400.2
ARPC1A	NM_001190996.2	c.941+519C>T		intron_variant			NP_001177925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC1A	ENST00000262942.10	c.983+519C>T		intron_variant		1	NM_006409.4	ENSP00000262942.5
ENSG00000284292	ENST00000638617.1	c.983+519C>T		intron_variant		5		ENSP00000491073.1

Frequencies

GnomAD3 genomes AF: 0.0829 AC: 12570 AN: 151678 Hom.: 715 Cov.: 31

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.: 18 Cov.: 0 AF XY: 0.0541 AC XY: 307 AN XY: 5678

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.0507

Gnomad4 ASJ exome AF: 0.0615

Gnomad4 EAS exome AF: 0.00326

Gnomad4 SAS exome AF: 0.0807

Gnomad4 FIN exome AF: 0.0571

Gnomad4 NFE exome AF: 0.0439

Gnomad4 OTH exome AF: 0.0440

GnomAD4 genome AF: 0.0830 AC: 12597 AN: 151772 Hom.: 719 Cov.: 31 AF XY: 0.0841 AC XY: 6235 AN XY: 74138

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.0537

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.0661

Gnomad4 NFE AF: 0.0463

Gnomad4 OTH AF: 0.0821

Alfa AF: 0.0499 Hom.: 301

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
DANN	Benign	0.36

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

LitVar

Other links and lift over

dbSNP: rs740160; hg19: chr7-98957880;