dbSNP rs11692435: ACTR1B:p.Ala143Val (chr2-97658891-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BA1

The NM_005735.4(ACTR1B):c.428C>T(p.Ala143Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 1,613,986 control chromosomes in the GnomAD database, including 6,471 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 0.065 ( 646 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5825 hom. )

Consequence

ACTR1B
NM_005735.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.86

Publications

57 publications found

Variant links:

Genes affected

ACTR1B (HGNC:168): (actin related protein 1B) This gene encodes a 42.3 kD subunit of dynactin, a macromolecular complex consisting of 10 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein and is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit, like ACTR1A, is an actin-related protein. These two proteins, which are of equal length and share 90% amino acid identity, are present in a constant ratio of approximately 1:15 in the dynactin complex. [provided by RefSeq, Aug 2008]

ACTR1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR1B	NM_005735.4 link	c.428C>T	p.Ala143Val	missense_variant	Exon 5 of 11	ENST00000289228.7	NP_005726.1	P42025
ACTR1B	XM_017003116.2 link	c.296C>T	p.Ala99Val	missense_variant	Exon 5 of 11		XP_016858605.1
ACTR1B	XM_005263854.6 link	c.206C>T	p.Ala69Val	missense_variant	Exon 4 of 10		XP_005263911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACTR1B	ENST00000289228.7 link	c.428C>T	p.Ala143Val	missense_variant	Exon 5 of 11	1	NM_005735.4	ENSP00000289228.5	P42025
ACTR1B	ENST00000451664.1 link	n.454C>T		non_coding_transcript_exon_variant	Exon 5 of 7	5
ACTR1B	ENST00000460427.2 link	n.653C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0649

AC:

9874

AN:

152032

Hom.:

646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0813

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0851

Gnomad OTH

AF:

0.0511

GnomAD2 exomes

AF:

0.0700

AC:

17602

AN:

251390

AF XY:

0.0696

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.0249

Gnomad ASJ exome

AF:

0.0390

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.0887

Gnomad OTH exome

AF:

0.0624

GnomAD4 exome

AF:

0.0786

AC:

114874

AN:

1461836

Hom.:

5825

Cov.:

AF XY:

0.0768

AC XY:

55886

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0107

AC:

358

AN:

33480

American (AMR)

AF:

0.0257

AC:

1150

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0389

AC:

1017

AN:

26136

East Asian (EAS)

AF:

0.000176

AC:

AN:

39700

South Asian (SAS)

AF:

0.0165

AC:

1419

AN:

86258

European-Finnish (FIN)

AF:

0.234

AC:

12501

AN:

53394

Middle Eastern (MID)

AF:

0.00712

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0851

AC:

94637

AN:

1111986

Other (OTH)

AF:

0.0620

AC:

3744

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

6321

12642

18964

25285

31606

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3302

6604

9906

13208

16510

<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:

0.0649

AC:

9875

AN:

152150

Hom.:

646

Cov.:

AF XY:

0.0708

AC XY:

5263

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0119

AC:

494

AN:

41554

American (AMR)

AF:

0.0409

AC:

625

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0357

AC:

124

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.0141

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.246

AC:

2592

AN:

10544

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0851

AC:

5788

AN:

67988

Other (OTH)

AF:

0.0506

AC:

107

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

426

852

1279

1705

2131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0713

Hom.:

1742

Bravo

AF:

0.0485

TwinsUK

AF:

0.0831

AC:

308

ALSPAC

AF:

0.0825

AC:

318

ESP6500AA

AF:

0.0159

AC:

ESP6500EA

AF:

0.0833

AC:

716

ExAC

AF:

0.0689

AC:

8371

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

0.0033

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.81

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.96

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.36

MutationAssessor

Pathogenic

4.1

PhyloP100

9.9

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.85

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.36

MPC

1.2

ClinPred

0.089

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.71

Mutation Taster

=64/36

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.76

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.76

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over