chr11-119081661-A-G

Position:

• chr11-119081661-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000621676.5(VPS11):​c.*38A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,605,874 control chromosomes in the GnomAD database, including 124,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12576 hom., cov: 32)
  • Exomes 𝑓: 0.39 (112329 hom.)
• Consequence: VPS11 ENST00000621676.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.136

Genes affected

VPS11 (HGNC:14583): (VPS11 core subunit of CORVET and HOPS complexes) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps11 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4564395E-4).
• BP6: Variant 11-119081661-A-G is Benign according to our data. Variant chr11-119081661-A-G is described in ClinVar as [Benign]. Clinvar id is 1684212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS11	NM_021729.6	c.*38A>G		3_prime_UTR_variant	16/16	ENST00000621676.5	NP_068375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS11	ENST00000621676.5	c.*38A>G		3_prime_UTR_variant	16/16	1	NM_021729.6	ENSP00000481126	P1
VPS11	ENST00000614944.4	c.*38A>G		3_prime_UTR_variant	16/16	2		ENSP00000481807
VPS11	ENST00000524454.1	n.322A>G		non_coding_transcript_exon_variant	2/2	2
VPS11	ENST00000622309.4	n.3049A>G		non_coding_transcript_exon_variant	13/13	5

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60682 AN: 151976 Hom.: 12567 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.414

GnomAD3 exomes AF: 0.357 AC: 83663 AN: 234180 Hom.: 15703 AF XY: 0.362 AC XY: 46146 AN XY: 127550

Gnomad AFR exome AF: 0.479

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.178

Gnomad SAS exome AF: 0.362

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.402

Gnomad OTH exome AF: 0.376

GnomAD4 exome AF: 0.389 AC: 565556 AN: 1453780 Hom.: 112329 Cov.: 36 AF XY: 0.389 AC XY: 280853 AN XY: 722272

Gnomad4 AFR exome AF: 0.478

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.415

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.399 AC: 60716 AN: 152094 Hom.: 12576 Cov.: 32 AF XY: 0.391 AC XY: 29053 AN XY: 74338

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.415

Alfa AF: 0.397 Hom.: 9872

Bravo AF: 0.404

TwinsUK AF: 0.398 AC: 1476

ALSPAC AF: 0.389 AC: 1498

ESP6500AA AF: 0.470 AC: 1924

ESP6500EA AF: 0.407 AC: 3397

ExAC AF: 0.357 AC: 43145

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dystonia 32 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Hypomyelinating leukodystrophy 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.46
DEOGEN2	Benign	0.0061	T
FATHMM_MKL	Benign	0.028	N
MetaRNN	Benign	0.00015	T
Sift4G	Benign	0.061	T
Vest4		0.020
GERP RS		-1.9

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: rs4614; hg19: chr11-118952371;