dbSNP rs78946357: ARL13B:c.1025-48G>A (chr3-94049358-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001174150.2(ARL13B):c.1025-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,110,448 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 107 hom. )

Consequence

ARL13B
NM_001174150.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.696

Publications

1 publications found

Variant links:

Genes affected

ARL13B (HGNC:25419): (ADP ribosylation factor like GTPase 13B) This gene encodes a member of the ADP-ribosylation factor-like family. The encoded protein is a small GTPase that contains both N-terminal and C-terminal guanine nucleotide-binding motifs. This protein is localized in the cilia and plays a role in cilia formation and in maintenance of cilia. Mutations in this gene are the cause of Joubert syndrome 8. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

ARL13B links:

DHFR2 (HGNC:27309): (dihydrofolate reductase 2) Enables dihydrofolate reductase activity and mRNA binding activity. Involved in tetrahydrofolate metabolic process and thymidine biosynthetic process. Located in mitochondrial inner membrane and mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

DHFR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-94049358-G-A is Benign according to our data. Variant chr3-94049358-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 263012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.06 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL13B	NM_001174150.2 link	c.1025-48G>A		intron_variant	Intron 7 of 9	ENST00000394222.8	NP_001167621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL13B	ENST00000394222.8 link	c.1025-48G>A		intron_variant	Intron 7 of 9	1	NM_001174150.2	ENSP00000377769.3

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

537

AN:

151778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00852

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0535

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.00447

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00767

AC:

1642

AN:

214192

AF XY:

0.00657

show subpopulations

Gnomad AFR exome

AF:

0.000351

Gnomad AMR exome

AF:

0.0218

Gnomad ASJ exome

AF:

0.00287

Gnomad EAS exome

AF:

0.0459

Gnomad FIN exome

AF:

0.00554

Gnomad NFE exome

AF:

0.000715

Gnomad OTH exome

AF:

0.00699

GnomAD4 exome

AF:

0.00418

AC:

4011

AN:

958552

Hom.:

107

Cov.:

AF XY:

0.00398

AC XY:

1967

AN XY:

493816

show subpopulations

African (AFR)

AF:

0.000311

AC:

AN:

22530

American (AMR)

AF:

0.0196

AC:

708

AN:

36044

Ashkenazi Jewish (ASJ)

AF:

0.00353

AC:

AN:

21538

East Asian (EAS)

AF:

0.0621

AC:

2278

AN:

36682

South Asian (SAS)

AF:

0.00269

AC:

182

AN:

67540

European-Finnish (FIN)

AF:

0.00564

AC:

290

AN:

51428

Middle Eastern (MID)

AF:

0.00171

AC:

AN:

4670

European-Non Finnish (NFE)

AF:

0.000434

AC:

293

AN:

674978

Other (OTH)

AF:

0.00392

AC:

169

AN:

43142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

171

342

513

684

855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.00354

AC:

537

AN:

151896

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

273

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41442

American (AMR)

AF:

0.00864

AC:

132

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3462

East Asian (EAS)

AF:

0.0534

AC:

276

AN:

5170

South Asian (SAS)

AF:

0.00292

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00447

AC:

AN:

10506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000618

AC:

AN:

67918

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.00428

Asia WGS

AF:

0.0230

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 01, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.0

(source)

DANN

Benign

0.60

PhyloP100

0.70

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over