2-113909917-C-G

Variant names:

• chr2-113909917-C-G
• rs11890727
• NM_005721.5:c.45-3255C>G

Variant summary

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

The NM_005721.5(ACTR3):​c.45-3255C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,948 control chromosomes in the GnomAD database, including 11,107 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 0.30 (11107 hom., cov: 31)
• Consequence: ACTR3 NM_005721.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421

Genes affected

ACTR3 (HGNC:170): (actin related protein 3) The specific function of this gene has not yet been determined; however, the protein it encodes is known to be a major constituent of the ARP2/3 complex. This complex is located at the cell surface and is essential to cell shape and motility through lamellipodial actin assembly and protrusion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

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 = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR3	NM_005721.5	c.45-3255C>G		intron_variant	Intron 1 of 11	ENST00000263238.7	NP_005712.1
ACTR3	NM_001277140.1	c.-109-3255C>G		intron_variant	Intron 1 of 11		NP_001264069.1
ACTR3	NR_102318.1	n.391-3255C>G		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTR3	ENST00000263238.7	c.45-3255C>G		intron_variant	Intron 1 of 11	1	NM_005721.5	ENSP00000263238.2

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45207 AN: 151830 Hom.: 11068 Cov.: 31

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45305 AN: 151948 Hom.: 11107 Cov.: 31 AF XY: 0.293 AC XY: 21788 AN XY: 74242

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.245

Alfa AF: 0.108 Hom.: 228

Bravo AF: 0.322

Asia WGS AF: 0.345 AC: 1201 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	0.95
DANN	Benign	0.51

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: rs11890727; hg19: chr2-114667494;