rs255758

Positions:

• chr5-54015672-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019087.3(ARL15):​c.462+97530G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 151,988 control chromosomes in the GnomAD database, including 39,508 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39508 hom., cov: 31)
• Consequence: ARL15 NM_019087.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL15	NM_019087.3	c.462+97530G>T		intron_variant		ENST00000504924.6	NP_061960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL15	ENST00000504924.6	c.462+97530G>T		intron_variant		1	NM_019087.3	ENSP00000433427	P1
ARL15	ENST00000502271.5	c.-76+97530G>T		intron_variant		1		ENSP00000473508
ARL15	ENST00000507646.2	c.462+97530G>T		intron_variant		5		ENSP00000432680
ARL15	ENST00000510591.6	n.535+97530G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109099 AN: 151870 Hom.: 39471 Cov.: 31

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.727

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.718 AC: 109187 AN: 151988 Hom.: 39508 Cov.: 31 AF XY: 0.719 AC XY: 53449 AN XY: 74292

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.722

Alfa AF: 0.743 Hom.: 27884

Bravo AF: 0.722

Asia WGS AF: 0.780 AC: 2711 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.37
DANN	Benign	0.39

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: rs255758; hg19: chr5-53311502; COSMIC: COSV72289573;