7-99385726-C-T

Variant names:

• chr7-99385726-C-T
• rs1242747091
• NM_005720.4:c.12C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 4P and 3B. PM2 PP3_Moderate BP6_Moderate BP7

The NM_005720.4(ARPC1B):​c.12C>T​(p.His4His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ARPC1B NM_005720.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.99
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.47
• BP6: Variant 7-99385726-C-T is Benign according to our data. Variant chr7-99385726-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1630688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.99 with no splicing effect.

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.12C>T	p.His4His	synonymous	Exon 2 of 10	NP_005711.1	A4D275

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC1B	ENST00000646101.2	MANE Select	c.12C>T	p.His4His	synonymous	Exon 2 of 10	ENSP00000496599.1	O15143
	ENSG00000284292	ENST00000638617.1	TSL:5	c.1008C>T	p.His336His	synonymous	Exon 9 of 17	ENSP00000491073.1	A0A1W2PNV4
	ARPC1B	ENST00000970476.1		c.12C>T	p.His4His	synonymous	Exon 2 of 11	ENSP00000640535.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 243588 AF XY: 0.00

Gnomad AFR exome AF: 0.0000642

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1458710 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 725440

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 85550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111394

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000604 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Likely 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	Pathogenic	0.47
CADD	Benign	13
DANN	Uncertain	1.0
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=68/132	disease causing (fs/PTC)

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: rs1242747091; hg19: chr7-98983349;