Variant 3-93980374-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001174150.2(ARL13B):c.-50C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,604,612 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

ARL13B
NM_001174150.2 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.50

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 3-93980374-C-A is Benign according to our data. Variant chr3-93980374-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 346906.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00172 (262/152266) while in subpopulation NFE AF= 0.00212 (144/68022). AF 95% confidence interval is 0.00183. There are 1 homozygotes in gnomad4. There are 160 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL13B	NM_001174150.2 linkuse as main transcript	c.-50C>A		5_prime_UTR_variant	1/10	ENST00000394222.8	NP_001167621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL13B	ENST00000394222.8 linkuse as main transcript	c.-50C>A		5_prime_UTR_variant	1/10	1	NM_001174150.2	ENSP00000377769	P1	Q3SXY8-1

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

262

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00913

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00175

AC:

430

AN:

245850

Hom.:

AF XY:

0.00172

AC XY:

229

AN XY:

133490

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.00759

Gnomad NFE exome

AF:

0.00220

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00171

AC:

2478

AN:

1452346

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1177

AN XY:

723066

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000510

Gnomad4 FIN exome

AF:

0.00783

Gnomad4 NFE exome

AF:

0.00177

Gnomad4 OTH exome

AF:

0.00115

GnomAD4 genome

AF:

0.00172

AC:

262

AN:

152266

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00913

Gnomad4 NFE

AF:

0.00212

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.00102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 27, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.0

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over