rs1802295

Positions:

• chr10-69171718-C-T

Variant summary

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

The NM_004896.5(VPS26A):​c.*449C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 154,168 control chromosomes in the GnomAD database, including 4,689 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 0.22 (4603 hom., cov: 32)
  • Exomes 𝑓: 0.27 (86 hom.)
• Consequence: VPS26A NM_004896.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411

Genes affected

VPS26A (HGNC:12711): (VPS26 retromer complex component A) This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS26A	NM_004896.5	c.*449C>T		3_prime_UTR_variant	9/9	ENST00000263559.11	NP_004887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS26A	ENST00000263559.11	c.*449C>T		3_prime_UTR_variant	9/9	1	NM_004896.5	ENSP00000263559.6
VPS26A	ENST00000373382.5	c.*449C>T		3_prime_UTR_variant	10/10	5		ENSP00000362480.1
VPS26A	ENST00000395098.5	c.*534C>T		3_prime_UTR_variant	8/8	5		ENSP00000378532.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33473 AN: 151990 Hom.: 4601 Cov.: 32

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.268 AC: 552 AN: 2060 Hom.: 86 Cov.: 0 AF XY: 0.262 AC XY: 289 AN XY: 1102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.0909

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.220 AC: 33476 AN: 152108 Hom.: 4603 Cov.: 32 AF XY: 0.220 AC XY: 16350 AN XY: 74350

Gnomad4 AFR AF: 0.0571

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.218

Alfa AF: 0.286 Hom.: 14438

Bravo AF: 0.207

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.0
DANN	Benign	0.52

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: rs1802295; hg19: chr10-70931474;