rs12256853

Variant names:

• chr10-69170604-A-G
• rs12256853
• NM_004896.5:c.871-552A>G

Variant summary

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

The NM_004896.5(VPS26A):​c.871-552A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,064 control chromosomes in the GnomAD database, including 3,938 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 (3938 hom., cov: 32)
• Consequence: VPS26A NM_004896.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 9 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS26A	NM_004896.5	c.871-552A>G		intron_variant	Intron 8 of 8	ENST00000263559.11	NP_004887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS26A	ENST00000263559.11	c.871-552A>G		intron_variant	Intron 8 of 8	1	NM_004896.5	ENSP00000263559.6

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33375 AN: 151946 Hom.: 3932 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0342

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.220 AC: 33397 AN: 152064 Hom.: 3938 Cov.: 32 AF XY: 0.218 AC XY: 16215 AN XY: 74346

African (AFR) AF: 0.245 AC: 10175 AN: 41472

American (AMR) AF: 0.147 AC: 2250 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3472

East Asian (EAS) AF: 0.0341 AC: 177 AN: 5190

South Asian (SAS) AF: 0.132 AC: 635 AN: 4818

European-Finnish (FIN) AF: 0.328 AC: 3457 AN: 10552

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15515 AN: 67962

Other (OTH) AF: 0.180 AC: 381 AN: 2116

Alfa AF: 0.210 Hom.: 5559

Bravo AF: 0.208

Asia WGS AF: 0.0930 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.3
DANN	Benign	0.34
PhyloP100		-0.49
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: rs12256853; hg19: chr10-70930360;