dbSNP rs6642: ACTR3:c.*501G>A (chr2-113957956-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005721.5(ACTR3):c.*501G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,620 control chromosomes in the GnomAD database, including 20,296 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 0.47 ( 20170 hom., cov: 31)

Exomes 𝑓: 0.60 ( 126 hom. )

Consequence

ACTR3
NM_005721.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.56

Publications

10 publications found

Variant links:

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]

ACTR3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005721.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTR3	NM_005721.5	MANE Select	c.*501G>A	3_prime_UTR	Exon 12 of 12	NP_005712.1	P61158
ACTR3	NM_001277140.1		c.*501G>A	3_prime_UTR	Exon 12 of 12	NP_001264069.1	B4DXW1
ACTR3	NR_102318.1		n.1979G>A	non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACTR3	ENST00000263238.7	TSL:1 MANE Select	c.*501G>A	3_prime_UTR	Exon 12 of 12	ENSP00000263238.2	P61158
ACTR3	ENST00000868069.1		c.*501G>A	3_prime_UTR	Exon 13 of 13	ENSP00000538128.1
ACTR3	ENST00000868078.1		c.*501G>A	3_prime_UTR	Exon 13 of 13	ENSP00000538137.1

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70699

AN:

151828

Hom.:

20177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.691

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.676

Gnomad NFE

AF:

0.629

Gnomad OTH

AF:

0.512

GnomAD4 exome

AF:

0.596

AC:

402

AN:

674

Hom.:

126

Cov.:

AF XY:

0.607

AC XY:

215

AN XY:

354

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.517

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.0833

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.704

AC:

159

AN:

226

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.580

AC:

188

AN:

324

Other (OTH)

AF:

0.286

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.465

AC:

70684

AN:

151946

Hom.:

20170

Cov.:

AF XY:

0.469

AC XY:

34842

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.147

AC:

6113

AN:

41452

American (AMR)

AF:

0.469

AC:

7146

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.691

AC:

2394

AN:

3464

East Asian (EAS)

AF:

0.125

AC:

648

AN:

5178

South Asian (SAS)

AF:

0.523

AC:

2519

AN:

4818

European-Finnish (FIN)

AF:

0.686

AC:

7235

AN:

10552

Middle Eastern (MID)

AF:

0.662

AC:

192

AN:

290

European-Non Finnish (NFE)

AF:

0.629

AC:

42698

AN:

67918

Other (OTH)

AF:

0.509

AC:

1077

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1576

3153

4729

6306

7882

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.488

Hom.:

4105

Bravo

AF:

0.432

Asia WGS

AF:

0.316

AC:

1099

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over