rs7936592

Variant names:

• chr11-134245221-T-C
• rs7936592
• NM_052875.5:c.864+141T>C

Variant summary

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

The NM_052875.5(VPS26B):​c.864+141T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0525 in 1,359,348 control chromosomes in the GnomAD database, including 4,662 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 0.12 (2225 hom., cov: 33)
  • Exomes 𝑓: 0.045 (2437 hom.)
• Consequence: VPS26B NM_052875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 2 publications found

Genes affected

VPS26B (HGNC:28119): (VPS26 retromer complex component B) Predicted to be involved in intracellular protein transport and retrograde transport, endosome to Golgi. Predicted to act upstream of or within cellular response to interferon-gamma. Predicted to be located in early endosome and late endosome. Predicted to be part of retromer complex. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052875.5. 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
	VPS26B	NM_052875.5	MANE Select	c.864+141T>C		intron	N/A	NP_443107.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS26B	ENST00000281187.10	TSL:1 MANE Select	c.864+141T>C		intron	N/A	ENSP00000281187.5
	VPS26B	ENST00000525095.2	TSL:5	c.864+141T>C		intron	N/A	ENSP00000434162.2
	VPS26B	ENST00000531741.1	TSL:2	n.1229+141T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17584 AN: 152052 Hom.: 2220 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0555

Gnomad ASJ AF: 0.0283

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0908

GnomAD4 exome AF: 0.0445 AC: 53732 AN: 1207178 Hom.: 2437 AF XY: 0.0429 AC XY: 25427 AN XY: 592948

African (AFR) AF: 0.326 AC: 8719 AN: 26770

American (AMR) AF: 0.0374 AC: 931 AN: 24890

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 523 AN: 19080

East Asian (EAS) AF: 0.0000863 AC: 3 AN: 34766

South Asian (SAS) AF: 0.00687 AC: 436 AN: 63500

European-Finnish (FIN) AF: 0.0385 AC: 1317 AN: 34192

Middle Eastern (MID) AF: 0.0319 AC: 138 AN: 4328

European-Non Finnish (NFE) AF: 0.0411 AC: 38971 AN: 948636

Other (OTH) AF: 0.0528 AC: 2694 AN: 51016

GnomAD4 genome AF: 0.116 AC: 17626 AN: 152170 Hom.: 2225 Cov.: 33 AF XY: 0.111 AC XY: 8248 AN XY: 74396

African (AFR) AF: 0.315 AC: 13047 AN: 41462

American (AMR) AF: 0.0554 AC: 848 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0283 AC: 98 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00725 AC: 35 AN: 4826

European-Finnish (FIN) AF: 0.0423 AC: 448 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0432 AC: 2936 AN: 68018

Other (OTH) AF: 0.0899 AC: 190 AN: 2114

Alfa AF: 0.0839 Hom.: 2017

Bravo AF: 0.127

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.28
PhyloP100		0.38
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: rs7936592; hg19: chr11-134115115;