chr11-65039806-A-C

Variant names:

• chr11-65039806-A-C
• rs495935
• ENST00000301886.3:n.*1260A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000301886.3(ARL2-SNX15):​n.*1260A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,568,922 control chromosomes in the GnomAD database, including 8,212 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 0.11 (1197 hom., cov: 31)
  • Exomes 𝑓: 0.091 (7015 hom.)
• Consequence: ARL2-SNX15 ENST00000301886.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 9 publications found

Genes affected

ARL2-SNX15 (HGNC:49197): (ARL2-SNX15 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ADP-ribosylation factor-like 2 (ARL2) and sorting nexin 15 (SNX15) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

SNX15 (HGNC:14978): (sorting nexin 15) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. Overexpression of this gene results in a decrease in the processing of insulin and hepatocyte growth factor receptors to their mature subunits. This decrease is caused by the mislocalization of furin, the endoprotease responsible for cleavage of insulin and hepatocyte growth factor receptors. This protein is involved in endosomal trafficking from the plasma membrane to recycling endosomes or the trans-Golgi network. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ADP-ribosylation factor-like 2 (ARL2) gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000301886.3. 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
	SNX15	NM_013306.5	MANE Select	c.*14A>C		3_prime_UTR	Exon 8 of 8	NP_037438.2
	ARL2-SNX15	NR_037650.2		n.1650A>C		non_coding_transcript_exon	Exon 11 of 11
	SNX15	NM_147777.4		c.*14A>C		3_prime_UTR	Exon 7 of 7	NP_680086.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL2-SNX15	ENST00000301886.3	TSL:2	n.*1260A>C		non_coding_transcript_exon	Exon 11 of 11	ENSP00000476630.1
	SNX15	ENST00000377244.8	TSL:1 MANE Select	c.*14A>C		3_prime_UTR	Exon 8 of 8	ENSP00000366452.3
	ARL2-SNX15	ENST00000301886.3	TSL:2	n.*1260A>C		3_prime_UTR	Exon 11 of 11	ENSP00000476630.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16936 AN: 151992 Hom.: 1197 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.104 AC: 23774 AN: 229032 AF XY: 0.105

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.0440

Gnomad EAS exome AF: 0.0650

Gnomad FIN exome AF: 0.0553

Gnomad NFE exome AF: 0.0750

Gnomad OTH exome AF: 0.0884

GnomAD4 exome AF: 0.0905 AC: 128235 AN: 1416812 Hom.: 7015 Cov.: 24 AF XY: 0.0931 AC XY: 65721 AN XY: 705860

African (AFR) AF: 0.184 AC: 5971 AN: 32430

American (AMR) AF: 0.134 AC: 5756 AN: 42966

Ashkenazi Jewish (ASJ) AF: 0.0416 AC: 1068 AN: 25666

East Asian (EAS) AF: 0.0585 AC: 2288 AN: 39098

South Asian (SAS) AF: 0.207 AC: 17322 AN: 83486

European-Finnish (FIN) AF: 0.0552 AC: 2900 AN: 52534

Middle Eastern (MID) AF: 0.0658 AC: 375 AN: 5696

European-Non Finnish (NFE) AF: 0.0806 AC: 86713 AN: 1076182

Other (OTH) AF: 0.0994 AC: 5842 AN: 58754

GnomAD4 genome AF: 0.112 AC: 16966 AN: 152110 Hom.: 1197 Cov.: 31 AF XY: 0.112 AC XY: 8329 AN XY: 74390

African (AFR) AF: 0.186 AC: 7715 AN: 41476

American (AMR) AF: 0.124 AC: 1899 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.0585 AC: 303 AN: 5182

South Asian (SAS) AF: 0.225 AC: 1083 AN: 4804

European-Finnish (FIN) AF: 0.0494 AC: 525 AN: 10618

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0740 AC: 5032 AN: 67976

Other (OTH) AF: 0.104 AC: 219 AN: 2110

Alfa AF: 0.0909 Hom.: 185

Bravo AF: 0.119

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.9
DANN	Benign	0.56
PhyloP100		-0.23
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: rs495935; hg19: chr11-64807278;