Variant chr5-57482386-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTBL2	NM_001017992.4 linkuse as main transcript	c.322G>A	p.Glu108Lys	missense_variant	1/1	ENST00000423391.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTBL2	ENST00000423391.3 linkuse as main transcript	c.322G>A	p.Glu108Lys	missense_variant	1/1		NM_001017992.4	P1
RMEL3	ENST00000506106.1 linkuse as main transcript	n.120-11689C>T		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes

AF:

0.00637

AC:

1599

AN:

251008

Hom.:

AF XY:

0.00490

AC XY:

665

AN XY:

135638

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 SAS exome

AF:

0.000229

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

Gnomad4 AFR exome

AF:

0.0831

Gnomad4 AMR exome

AF:

0.00512

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000255

Gnomad4 OTH exome

AF:

0.00541

GnomAD4 genome

AF:

0.0238

AC:

3621

AN:

152176

Hom.:

170

Cov.:

AF XY:

0.0224

AC XY:

1669

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0819

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00417

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

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

MutationTaster

Benign

1.0

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

Varity_R

0.85

gMVP

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over