dbSNP rs3803185: ARL11:p.Cys148Arg (chr13-49630889-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_138450.6(ARL11):c.442T>C(p.Cys148Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,587,468 control chromosomes in the GnomAD database, including 186,259 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 12444 hom., cov: 31)

Exomes 𝑓: 0.48 ( 173815 hom. )

Consequence

ARL11
NM_138450.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.05

Publications

57 publications found

Variant links:

Genes affected

ARL11 (HGNC:24046): (ADP ribosylation factor like GTPase 11) This gene encodes a tumor suppressor related to the ADP-ribosylation factor (ARF) family of proteins. The encoded protein may play a role in apoptosis in a caspase-dependent manner. Polymorphisms in this gene have been associated with some familial cancers. [provided by RefSeq, May 2010]

ARL11 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=0.0010447502).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL11	NM_138450.6 link	c.442T>C	p.Cys148Arg	missense_variant	Exon 2 of 2	ENST00000282026.2	NP_612459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL11	ENST00000282026.2 link	c.442T>C	p.Cys148Arg	missense_variant	Exon 2 of 2	1	NM_138450.6	ENSP00000282026.1
ARL11	ENST00000490932.1 link	n.159+790T>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

56036

AN:

151852

Hom.:

12433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.398

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.400

GnomAD2 exomes

AF:

0.391

AC:

93390

AN:

238702

AF XY:

0.394

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.351

Gnomad ASJ exome

AF:

0.428

Gnomad EAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.405

Gnomad NFE exome

AF:

0.507

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.479

AC:

688274

AN:

1435498

Hom.:

173815

Cov.:

AF XY:

0.474

AC XY:

336245

AN XY:

709992

show subpopulations

African (AFR)

AF:

0.126

AC:

4129

AN:

32798

American (AMR)

AF:

0.355

AC:

15109

AN:

42616

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

10659

AN:

24778

East Asian (EAS)

AF:

0.183

AC:

7191

AN:

39218

South Asian (SAS)

AF:

0.254

AC:

21328

AN:

84108

European-Finnish (FIN)

AF:

0.418

AC:

21938

AN:

52494

Middle Eastern (MID)

AF:

0.398

AC:

2251

AN:

5652

European-Non Finnish (NFE)

AF:

0.529

AC:

579253

AN:

1094832

Other (OTH)

AF:

0.448

AC:

26416

AN:

59002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

20406

40812

61219

81625

102031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16456

32912

49368

65824

82280

<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:

0.369

AC:

56047

AN:

151970

Hom.:

12444

Cov.:

AF XY:

0.359

AC XY:

26669

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.138

AC:

5732

AN:

41498

American (AMR)

AF:

0.398

AC:

6075

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

1443

AN:

3468

East Asian (EAS)

AF:

0.187

AC:

960

AN:

5140

South Asian (SAS)

AF:

0.249

AC:

1201

AN:

4816

European-Finnish (FIN)

AF:

0.379

AC:

3998

AN:

10542

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.520

AC:

35347

AN:

67932

Other (OTH)

AF:

0.403

AC:

848

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1597

3195

4792

6390

7987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.440

Hom.:

30496

Bravo

AF:

0.362

TwinsUK

AF:

0.530

AC:

1964

ALSPAC

AF:

0.538

AC:

2072

ESP6500AA

AF:

0.146

AC:

643

ESP6500EA

AF:

0.514

AC:

4418

ExAC

AF:

0.383

AC:

46510

Asia WGS

AF:

0.224

AC:

780

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.023

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

-2.0

PrimateAI

Benign

0.44

PROVEAN

Benign

0.35

REVEL

Benign

0.19

Sift

Benign

0.33

Sift4G

Benign

0.52

Polyphen

0.0010

Vest4

0.0060

MPC

0.27

ClinPred

0.034

GERP RS

-11

Varity_R

0.14

gMVP

0.24

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over