3-93980161-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001174150.2(ARL13B):c.-263C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00757 in 634,016 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (25 hom.)
• Consequence: ARL13B NM_001174150.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 3-93980161-C-T is Benign according to our data. Variant chr3-93980161-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 346901.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00691 (1052/152332) while in subpopulation NFE AF= 0.0112 (765/68026). AF 95% confidence interval is 0.0106. There are 5 homozygotes in gnomad4. There are 469 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL13B	NM_001174150.2	c.-263C>T		5_prime_UTR_variant	1/10	ENST00000394222.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL13B	ENST00000394222.8	c.-263C>T		5_prime_UTR_variant	1/10	1	NM_001174150.2	P1

Frequencies

GnomAD3 genomes AF: 0.00692 AC: 1054 AN: 152214 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00680 AC: 719 AN: 105692 Hom.: 3 AF XY: 0.00674 AC XY: 382 AN XY: 56672

Gnomad AFR exome AF: 0.00134

Gnomad AMR exome AF: 0.00682

Gnomad ASJ exome AF: 0.0111

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00202

Gnomad FIN exome AF: 0.000283

Gnomad NFE exome AF: 0.0112

Gnomad OTH exome AF: 0.00683

GnomAD4 exome AF: 0.00778 AC: 3748 AN: 481684 Hom.: 25 Cov.: 4 AF XY: 0.00745 AC XY: 1924 AN XY: 258218

Gnomad4 AFR exome AF: 0.00179

Gnomad4 AMR exome AF: 0.00661

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00247

Gnomad4 FIN exome AF: 0.00174

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.00788

GnomAD4 genome AF: 0.00691 AC: 1052 AN: 152332 Hom.: 5 Cov.: 32 AF XY: 0.00630 AC XY: 469 AN XY: 74500

Gnomad4 AFR AF: 0.00176

Gnomad4 AMR AF: 0.00784

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00437 Hom.: 1

Bravo AF: 0.00736

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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	-0.57
Cadd	Benign	12
Dann	Benign	0.92

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

Other links and lift over

dbSNP: rs143828740; hg19: chr3-93699005;