Genetic Variant ARL15:c.463-64851T>C (chr5-53951564-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000504924.6(ARL15):c.463-64851T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000309 in 323,698 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

ARL15
ENST00000504924.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.661

Publications

4 publications found

Variant links:

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]

ARL15 links:

MIR581 (HGNC:32837): (microRNA 581) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR581 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000504924.6. 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
	ARL15	NM_019087.3	MANE Select	c.463-64851T>C		intron	N/A	NP_061960.1
	MIR581	NR_030307.1		n.36T>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARL15	ENST00000504924.6	TSL:1 MANE Select	c.463-64851T>C	intron	N/A	ENSP00000433427.1
ARL15	ENST00000502271.5	TSL:1	c.-75-64851T>C	intron	N/A	ENSP00000473508.1
MIR581	ENST00000384895.1	TSL:6	n.36T>C	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000309

AC:

AN:

323698

Hom.:

Cov.:

AF XY:

0.00000545

AC XY:

AN XY:

183502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8718

American (AMR)

AF:

0.00

AC:

AN:

28182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11028

East Asian (EAS)

AF:

0.00

AC:

AN:

10140

South Asian (SAS)

AF:

0.00

AC:

AN:

59934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1754

European-Non Finnish (NFE)

AF:

0.00000621

AC:

AN:

161030

Other (OTH)

AF:

0.00

AC:

AN:

14324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.9

(source)

DANN

Benign

0.77

PhyloP100

0.66

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over