2-113909917-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005721.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR3	NM_005721.5	MANE Select	c.45-3255C>G		intron	N/A	NP_005712.1
	ACTR3	NM_001277140.1		c.-109-3255C>G		intron	N/A	NP_001264069.1
	ACTR3	NR_102318.1		n.391-3255C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR3	ENST00000263238.7	TSL:1 MANE Select	c.45-3255C>G		intron	N/A	ENSP00000263238.2
	ACTR3	ENST00000868069.1		c.45-3255C>G		intron	N/A	ENSP00000538128.1
	ACTR3	ENST00000868078.1		c.45-3255C>G		intron	N/A	ENSP00000538137.1

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

African (AFR) AF: 0.672 AC: 27841 AN: 41430

American (AMR) AF: 0.213 AC: 3256 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3464

East Asian (EAS) AF: 0.394 AC: 2040 AN: 5174

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4818

European-Finnish (FIN) AF: 0.131 AC: 1379 AN: 10524

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8619 AN: 67944

Other (OTH) AF: 0.245 AC: 517 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.95
DANN	Benign	0.51
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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: rs11890727; hg19: chr2-114667494;