Genetic Variant ACTBL2:p.Glu108Lys (chr5-57482386-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001017992.4(ACTBL2):c.322G>A(p.Glu108Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00451 in 1,614,024 control chromosomes in the GnomAD database, including 311 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 0.024 ( 170 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 141 hom. )

Consequence

ACTBL2
NM_001017992.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.14

Publications

5 publications found

Variant links:

Genes affected

ACTBL2 (HGNC:17780): (actin beta like 2) Predicted to enable protein kinase binding activity. Predicted to be a structural constituent of postsynaptic actin cytoskeleton. Predicted to be involved in axonogenesis and cell motility. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACTBL2 links:

RMEL3 (HGNC:53975): (enriched in melanoma 3)

RMEL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.009886682).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017992.4. 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
	ACTBL2	NM_001017992.4	MANE Select	c.322G>A	p.Glu108Lys	missense	Exon 1 of 1	NP_001017992.1
	RMEL3	NR_186596.1		n.73-11689C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ACTBL2	ENST00000423391.3	TSL:6 MANE Select	c.322G>A	p.Glu108Lys	missense	Exon 1 of 1	ENSP00000416706.1
RMEL3	ENST00000506106.1	TSL:2	n.120-11689C>T		intron	N/A
RMEL3	ENST00000771489.1		n.274-6268C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3615

AN:

152056

Hom.:

170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0819

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00637

AC:

1599

AN:

251008

AF XY:

0.00490

show subpopulations

Gnomad AFR exome

AF:

0.0838

Gnomad AMR exome

AF:

0.00471

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000388

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00251

AC:

3665

AN:

1461848

Hom.:

141

Cov.:

AF XY:

0.00218

AC XY:

1584

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.0831

AC:

2782

AN:

33480

American (AMR)

AF:

0.00512

AC:

229

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.000197

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00381

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000255

AC:

284

AN:

1112002

Other (OTH)

AF:

0.00541

AC:

327

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

254

508

763

1017

1271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.0238

AC:

3621

AN:

152176

Hom.:

170

Cov.:

AF XY:

0.0224

AC XY:

1669

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0819

AC:

3396

AN:

41490

American (AMR)

AF:

0.0111

AC:

170

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68018

Other (OTH)

AF:

0.0152

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

168

337

505

674

842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.00833

Hom.:

Bravo

AF:

0.0268

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0772

AC:

340

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00779

AC:

946

Asia WGS

AF:

0.00434

AC:

AN:

3474

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

Eigen

Pathogenic

0.77

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0099

MetaSVM

Uncertain

-0.28

MutationAssessor

Pathogenic

4.5

PhyloP100

6.1

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.1

REVEL

Pathogenic

0.84

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.69

MVP

0.79

MPC

0.40

ClinPred

0.076

GERP RS

4.0

PromoterAI

-0.0030

Neutral

(source)

Varity_R

0.85

gMVP

0.90

Mutation Taster

=92/8

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

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