rs11755

Positions:

• chr1-183627001-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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]

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 = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARPC5	NM_005717.4	c.*531T>C		3_prime_UTR_variant	4/4	ENST00000359856.11
ARPC5	NM_001270439.2	c.*531T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARPC5	ENST00000359856.11	c.*531T>C		3_prime_UTR_variant	4/4	1	NM_005717.4	P3
ARPC5	ENST00000294742.6	c.*531T>C		3_prime_UTR_variant	4/4	1		A1
ARPC5	ENST00000367534.5	c.393+3460T>C		intron_variant		3
ARPC5	ENST00000462965.1	n.1648T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80727 AN: 151964 Hom.: 23015 Cov.: 32

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.: 0 AF XY: 0.410 AC XY: 353 AN XY: 860

Gnomad4 AMR exome AF: 0.396

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.413

GnomAD4 genome AF: 0.532 AC: 80847 AN: 152082 Hom.: 23073 Cov.: 32 AF XY: 0.527 AC XY: 39173 AN XY: 74324

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.514

Alfa AF: 0.465 Hom.: 27891

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
DANN	Benign	0.66

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: rs11755; hg19: chr1-183596136;