rs714459

Variant names:

• chr5-54583746-T-A
• rs714459
• XM_017008997.2:c.1622-22657T>A

Variant summary

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

The XM_017008997.2(SNX18):​c.1622-22657T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,112 control chromosomes in the GnomAD database, including 18,738 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 0.48 (18738 hom., cov: 33)
• Consequence: SNX18 XM_017008997.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 0 publications found

Genes affected

SNX18 (HGNC:19245): (sorting nexin 18) 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. This protein does not contain a coiled coil region, like some family members, but contains a SH3 domain. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX18	XM_017008997.2	c.1622-22657T>A		intron_variant	Intron 1 of 1		XP_016864486.1
SNX18	XR_001741987.2	n.1816-22657T>A		intron_variant	Intron 1 of 2
SNX18	XR_007058577.1	n.1816-22657T>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72783 AN: 151994 Hom.: 18712 Cov.: 33

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.479 AC: 72861 AN: 152112 Hom.: 18738 Cov.: 33 AF XY: 0.476 AC XY: 35435 AN XY: 74372

African (AFR) AF: 0.680 AC: 28209 AN: 41494

American (AMR) AF: 0.436 AC: 6665 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1413 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1735 AN: 5178

South Asian (SAS) AF: 0.574 AC: 2772 AN: 4826

European-Finnish (FIN) AF: 0.332 AC: 3507 AN: 10566

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26978 AN: 67964

Other (OTH) AF: 0.485 AC: 1024 AN: 2112

Alfa AF: 0.439 Hom.: 2178

Bravo AF: 0.491

Asia WGS AF: 0.506 AC: 1760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.019
DANN	Benign	0.50
PhyloP100		-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs714459; hg19: chr5-53879576; COSMIC: COSV60132615;