chr11-119081661-A-G

Variant names:

• chr11-119081661-A-G
• rs4614
• NM_021729.6:c.*38A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021729.6(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 NM_021729.6 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VPS11	NM_021729.6	c.*38A>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000621676.5	NP_068375.3

Ensembl

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

GnomAD2 exomes AF: 0.357 AC: 83663 AN: 234180 AF XY: 0.362

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 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 AC: 15922 AN: 33314

Gnomad4 AMR exome AF: 0.285 AC: 12414 AN: 43490

Gnomad4 ASJ exome AF: 0.415 AC: 10760 AN: 25924

Gnomad4 EAS exome AF: 0.141 AC: 5582 AN: 39520

Gnomad4 SAS exome AF: 0.360 AC: 30953 AN: 85868

Gnomad4 FIN exome AF: 0.290 AC: 15249 AN: 52672

Gnomad4 NFE exome AF: 0.406 AC: 449064 AN: 1107240

Gnomad4 Remaining exome AF: 0.389 AC: 23348 AN: 60082

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 AC: 0.475665 AN: 0.475665

Gnomad4 AMR AF: 0.347 AC: 0.347135 AN: 0.347135

Gnomad4 ASJ AF: 0.406 AC: 0.405889 AN: 0.405889

Gnomad4 EAS AF: 0.174 AC: 0.173635 AN: 0.173635

Gnomad4 SAS AF: 0.351 AC: 0.351307 AN: 0.351307

Gnomad4 FIN AF: 0.283 AC: 0.282962 AN: 0.282962

Gnomad4 NFE AF: 0.402 AC: 0.401589 AN: 0.401589

Gnomad4 OTH AF: 0.415 AC: 0.414611 AN: 0.414611

Alfa AF: 0.398 Hom.: 14493

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

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hypomyelinating leukodystrophy 12 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs4614; hg19: chr11-118952371; COSMIC: COSV107225326; COSMIC: COSV107225326;