NM_001174150.2:c.1025-48G>A

Variant names:

• chr3-94049358-G-A
• rs78946357
• NM_001174150.2:c.1025-48G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174150.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL13B	NM_001174150.2	MANE Select	c.1025-48G>A		intron	N/A	NP_001167621.1
	ARL13B	NM_182896.3		c.1025-48G>A		intron	N/A	NP_878899.1
	ARL13B	NM_001321328.2		c.980-48G>A		intron	N/A	NP_001308257.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL13B	ENST00000394222.8	TSL:1 MANE Select	c.1025-48G>A		intron	N/A	ENSP00000377769.3
	ARL13B	ENST00000471138.5	TSL:1	c.1025-48G>A		intron	N/A	ENSP00000420780.1
	ARL13B	ENST00000535334.5	TSL:1	c.716-48G>A		intron	N/A	ENSP00000445145.1

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

GnomAD2 exomes AF: 0.00767 AC: 1642 AN: 214192 AF XY: 0.00657

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

African (AFR) AF: 0.000311 AC: 7 AN: 22530

American (AMR) AF: 0.0196 AC: 708 AN: 36044

Ashkenazi Jewish (ASJ) AF: 0.00353 AC: 76 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: 8 AN: 4670

European-Non Finnish (NFE) AF: 0.000434 AC: 293 AN: 674978

Other (OTH) AF: 0.00392 AC: 169 AN: 43142

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

African (AFR) AF: 0.000265 AC: 11 AN: 41442

American (AMR) AF: 0.00864 AC: 132 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3462

East Asian (EAS) AF: 0.0534 AC: 276 AN: 5170

South Asian (SAS) AF: 0.00292 AC: 14 AN: 4802

European-Finnish (FIN) AF: 0.00447 AC: 47 AN: 10506

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 67918

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.60
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs78946357; hg19: chr3-93768202;