rs226849

chr16-19583771-G-Achr16-19583771-G-C

Variant summary

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

The NM_020314.7(VPS35L):c.639+2118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,726 control chromosomes in the GnomAD database, including 26,174 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 0.55 (26174 hom., cov: 30)
• Consequence: VPS35L NM_020314.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

Genes affected

VPS35L (HGNC:24641): (VPS35 endosomal protein sorting factor like) Involved in Golgi to plasma membrane transport and endocytic recycling. Located in endosome. Implicated in Ritscher-Schinzel syndrome. [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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS35L	NM_020314.7	c.639+2118G>A		intron_variant		ENST00000417362.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS35L	ENST00000417362.7	c.639+2118G>A		intron_variant		1	NM_020314.7	P1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83239 AN: 151606 Hom.: 26119 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.549 AC: 83350 AN: 151726 Hom.: 26174 Cov.: 30 AF XY: 0.547 AC XY: 40560 AN XY: 74110

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.530

Alfa AF: 0.502 Hom.: 3366

Bravo AF: 0.585

Asia WGS AF: 0.554 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	1.4
Dann	Benign	0.15

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: rs226849; hg19: chr16-19595093;