7-99385798-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005720.4(ARPC1B):​c.64+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 1,600,176 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00067 (7 hom.)
• Consequence: ARPC1B NM_005720.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.676
• Publications: 1 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 7-99385798-C-T is Benign according to our data. Variant chr7-99385798-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00187 (285/152266) while in subpopulation AFR AF = 0.00489 (203/41554). AF 95% confidence interval is 0.00433. There are 0 homozygotes in GnomAd4. There are 134 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

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>T		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>T		intron	N/A	ENSP00000496599.1	O15143
	ENSG00000284292	ENST00000638617.1	TSL:5	c.1060+20C>T		intron	N/A	ENSP00000491073.1	A0A1W2PNV4
	ARPC1B	ENST00000897885.1		c.84C>T	p.Ala28Ala	splice_region synonymous	Exon 2 of 10	ENSP00000567944.1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152148 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00105 AC: 235 AN: 223900 AF XY: 0.000965

Gnomad AFR exome AF: 0.00410

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00414

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000617

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.000669 AC: 968 AN: 1447910 Hom.: 7 Cov.: 31 AF XY: 0.000652 AC XY: 469 AN XY: 719280

African (AFR) AF: 0.00482 AC: 161 AN: 33396

American (AMR) AF: 0.00223 AC: 95 AN: 42630

Ashkenazi Jewish (ASJ) AF: 0.00376 AC: 97 AN: 25794

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: 0.00419 AC: 24 AN: 5728

European-Non Finnish (NFE) AF: 0.000453 AC: 502 AN: 1107662

Other (OTH) AF: 0.00148 AC: 89 AN: 59982

GnomAD4 genome AF: 0.00187 AC: 285 AN: 152266 Hom.: 0 Cov.: 31 AF XY: 0.00180 AC XY: 134 AN XY: 74436

African (AFR) AF: 0.00489 AC: 203 AN: 41554

American (AMR) AF: 0.00163 AC: 25 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68002

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00175 Hom.: 0

Bravo AF: 0.00236

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.69
PhyloP100		-0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs116514404; hg19: chr7-98983421;