5-54310465-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_019087.3(ARL15):c.15A>G(p.Arg5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 1,607,190 control chromosomes in the GnomAD database, including 565,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.86 (56236 hom., cov: 32)
  • Exomes 𝑓: 0.84 (509323 hom.)
• Consequence: ARL15 NM_019087.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.181

Genes affected

ARL15 (HGNC:25945): (ADP ribosylation factor like GTPase 15) Predicted to enable GTP binding activity and GTPase activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 5-54310465-T-C is Benign according to our data. Variant chr5-54310465-T-C is described in ClinVar as [Benign]. Clinvar id is 3060130.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-54310465-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.181 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL15	NM_019087.3	c.15A>G	p.Arg5=	synonymous_variant	1/5	ENST00000504924.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL15	ENST00000504924.6	c.15A>G	p.Arg5=	synonymous_variant	1/5	1	NM_019087.3	P1

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130404 AN: 152002 Hom.: 56185 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.839

GnomAD3 exomes AF: 0.817 AC: 192174 AN: 235304 Hom.: 78772 AF XY: 0.818 AC XY: 104443 AN XY: 127728

Gnomad AFR exome AF: 0.932

Gnomad AMR exome AF: 0.759

Gnomad ASJ exome AF: 0.757

Gnomad EAS exome AF: 0.710

Gnomad SAS exome AF: 0.791

Gnomad FIN exome AF: 0.850

Gnomad NFE exome AF: 0.843

Gnomad OTH exome AF: 0.816

GnomAD4 exome AF: 0.836 AC: 1216290 AN: 1455070 Hom.: 509323 Cov.: 61 AF XY: 0.835 AC XY: 603682 AN XY: 723038

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.753

Gnomad4 EAS exome AF: 0.720

Gnomad4 SAS exome AF: 0.795

Gnomad4 FIN exome AF: 0.852

Gnomad4 NFE exome AF: 0.845

Gnomad4 OTH exome AF: 0.827

GnomAD4 genome AF: 0.858 AC: 130508 AN: 152120 Hom.: 56236 Cov.: 32 AF XY: 0.856 AC XY: 63665 AN XY: 74340

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.833

Alfa AF: 0.843 Hom.: 72470

Bravo AF: 0.855

Asia WGS AF: 0.746 AC: 2593 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ARL15-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	14
Dann	Benign	0.79

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: rs35941; hg19: chr5-53606295; COSMIC: COSV72290403; COSMIC: COSV72290403;