5-54310465-T-C

Variant names:

• chr5-54310465-T-C
• rs35941
• NM_019087.3:c.15A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_019087.3(ARL15):​c.15A>G​(p.Arg5Arg) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.86 (56236 hom., cov: 32)
  • Exomes 𝑓: 0.84 (509323 hom.)
• Consequence: ARL15 NM_019087.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.181
• Publications: 22 publications found

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]

ENSG00000293676 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 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 VariationId is 3060130.Status of the report is no_assertion_criteria_provided, 0 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019087.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL15	NM_019087.3	MANE Select	c.15A>G	p.Arg5Arg	synonymous	Exon 1 of 5	NP_061960.1	Q9NXU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL15	ENST00000504924.6	TSL:1 MANE Select	c.15A>G	p.Arg5Arg	synonymous	Exon 1 of 5	ENSP00000433427.1	Q9NXU5
	ARL15	ENST00000502271.5	TSL:1	c.-437A>G		5_prime_UTR	Exon 1 of 5	ENSP00000473508.1	R4GN67
	ARL15	ENST00000505630.5	TSL:1	n.112A>G		non_coding_transcript_exon	Exon 1 of 4

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

GnomAD2 exomes AF: 0.817 AC: 192174 AN: 235304 AF XY: 0.818

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 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

African (AFR) AF: 0.932 AC: 31056 AN: 33310

American (AMR) AF: 0.767 AC: 33595 AN: 43824

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 19593 AN: 26008

East Asian (EAS) AF: 0.720 AC: 28344 AN: 39346

South Asian (SAS) AF: 0.795 AC: 67358 AN: 84718

European-Finnish (FIN) AF: 0.852 AC: 45056 AN: 52862

Middle Eastern (MID) AF: 0.776 AC: 4470 AN: 5760

European-Non Finnish (NFE) AF: 0.845 AC: 937079 AN: 1109094

Other (OTH) AF: 0.827 AC: 49739 AN: 60148

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

African (AFR) AF: 0.930 AC: 38634 AN: 41544

American (AMR) AF: 0.809 AC: 12367 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2615 AN: 3470

East Asian (EAS) AF: 0.721 AC: 3692 AN: 5122

South Asian (SAS) AF: 0.798 AC: 3843 AN: 4814

European-Finnish (FIN) AF: 0.859 AC: 9096 AN: 10586

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57503 AN: 67978

Other (OTH) AF: 0.833 AC: 1757 AN: 2110

Alfa AF: 0.843 Hom.: 97583

Bravo AF: 0.855

Asia WGS AF: 0.746 AC: 2593 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ARL15-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		0.18
PromoterAI		-0.010	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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