rs7936592

chr11-134245221-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS26B	NM_052875.5	c.864+141T>C		intron_variant		ENST00000281187.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS26B	ENST00000281187.10	c.864+141T>C		intron_variant		1	NM_052875.5	P1
VPS26B	ENST00000525095.2	c.864+141T>C		intron_variant		5		P1
VPS26B	ENST00000531741.1	n.1229+141T>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.326

Gnomad4 AMR exome AF: 0.0374

Gnomad4 ASJ exome AF: 0.0274

Gnomad4 EAS exome AF: 0.0000863

Gnomad4 SAS exome AF: 0.00687

Gnomad4 FIN exome AF: 0.0385

Gnomad4 NFE exome AF: 0.0411

Gnomad4 OTH exome AF: 0.0528

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

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.0554

Gnomad4 ASJ AF: 0.0283

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.0432

Gnomad4 OTH AF: 0.0899

Alfa AF: 0.0540 Hom.: 502

Bravo AF: 0.127

Asia WGS AF: 0.0300 AC: 104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	7.0
Dann	Benign	0.28

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: rs7936592; hg19: chr11-134115115;