rs78946357

chr3-94049358-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.696

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]

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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/exons	MANE	UniProt
ARL13B	NM_001174150.2	c.1025-48G>A		intron_variant		ENST00000394222.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL13B	ENST00000394222.8	c.1025-48G>A		intron_variant		1	NM_001174150.2	P1

Frequencies

GnomAD3 genomes AF: 0.00354 AC: 537 AN: 151778 Hom.: 17 Cov.: 32

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

GnomAD3 exomes AF: 0.00767 AC: 1642 AN: 214192 Hom.: 32 AF XY: 0.00657 AC XY: 764 AN XY: 116278

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 SAS exome AF: 0.00232

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.: 12 AF XY: 0.00398 AC XY: 1967 AN XY: 493816

Gnomad4 AFR exome AF: 0.000311

Gnomad4 AMR exome AF: 0.0196

Gnomad4 ASJ exome AF: 0.00353

Gnomad4 EAS exome AF: 0.0621

Gnomad4 SAS exome AF: 0.00269

Gnomad4 FIN exome AF: 0.00564

Gnomad4 NFE exome AF: 0.000434

Gnomad4 OTH exome AF: 0.00392

GnomAD4 genome AF: 0.00354 AC: 537 AN: 151896 Hom.: 18 Cov.: 32 AF XY: 0.00368 AC XY: 273 AN XY: 74242

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00864

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0534

Gnomad4 SAS AF: 0.00292

Gnomad4 FIN AF: 0.00447

Gnomad4 NFE AF: 0.000618

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00179 Hom.: 1

Bravo AF: 0.00428

Asia WGS AF: 0.0230 AC: 81 AN: 3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.0
Dann	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs78946357; hg19: chr3-93768202;