rs3776720

chr5-54000328-A-Gchr5-54000328-A-T

Variant summary

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

The NM_019087.3(ARL15):c.462+112874T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,012 control chromosomes in the GnomAD database, including 6,241 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 0.28 (6241 hom., cov: 32)
• Consequence: ARL15 NM_019087.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL15	NM_019087.3	c.462+112874T>C		intron_variant		ENST00000504924.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL15	ENST00000504924.6	c.462+112874T>C		intron_variant		1	NM_019087.3	P1
ARL15	ENST00000502271.5	c.-76+112874T>C		intron_variant		1
ARL15	ENST00000507646.2	c.462+112874T>C		intron_variant		5
ARL15	ENST00000510591.6	n.535+112874T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42693 AN: 151894 Hom.: 6235 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.281 AC: 42737 AN: 152012 Hom.: 6241 Cov.: 32 AF XY: 0.281 AC XY: 20904 AN XY: 74302

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.298

Alfa AF: 0.253 Hom.: 639

Bravo AF: 0.283

Asia WGS AF: 0.412 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.9
Dann	Benign	0.44

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: rs3776720; hg19: chr5-53296158; COSMIC: COSV72289476;