7-99385798-C-A

Variant names:

• chr7-99385798-C-A
• rs116514404
• NM_005720.4:c.64+20C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005720.4(ARPC1B):​c.64+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,916 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARPC1B NM_005720.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676
• Publications: 0 publications found

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]

ARPC1B Gene-Disease associations (from GenCC):

• platelet abnormalities with eosinophilia and immune-mediated inflammatory disease

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000284292 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005720.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC1B	NM_005720.4	MANE Select	c.64+20C>A		intron	N/A	NP_005711.1	A4D275

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC1B	ENST00000646101.2	MANE Select	c.64+20C>A		intron	N/A	ENSP00000496599.1	O15143
	ENSG00000284292	ENST00000638617.1	TSL:5	c.1060+20C>A		intron	N/A	ENSP00000491073.1	A0A1W2PNV4
	ARPC1B	ENST00000897885.1		c.84C>A	p.Ala28Ala	splice_region synonymous	Exon 2 of 10	ENSP00000567944.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447916 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719280

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.0000235 AC: 1 AN: 42632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25796

East Asian (EAS) AF: 0.00 AC: 0 AN: 39320

South Asian (SAS) AF: 0.00 AC: 0 AN: 84032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107664

Other (OTH) AF: 0.00 AC: 0 AN: 59982

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.36
DANN	Benign	0.68
PhyloP100		-0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs116514404; hg19: chr7-98983421;