rs3820553

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000081.4(LYST):c.1683A>G(p.Leu561Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,674 control chromosomes in the GnomAD database, including 124,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13180 hom., cov: 32)

Exomes 𝑓: 0.38 ( 111243 hom. )

Consequence

LYST
NM_000081.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -0.429

Publications

16 publications found

Variant links:

Genes affected

LYST (HGNC:1968): (lysosomal trafficking regulator) This gene encodes a protein that regulates intracellular protein trafficking in endosomes, and may be involved in pigmentation. Mutations in this gene are associated with Chediak-Higashi syndrome, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants, though the full-length nature of some of these variants has not been determined. [provided by RefSeq, Apr 2013]

LYST Gene-Disease associations (from GenCC):

Chediak-Higashi syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P
attenuated Chédiak-Higashi syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LYST links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-235809135-T-C is Benign according to our data. Variant chr1-235809135-T-C is described in ClinVar as [Benign]. Clinvar id is 254912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.429 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.1683A>G	p.Leu561Leu	synonymous_variant	Exon 5 of 53	ENST00000389793.7	NP_000072.2	Q99698-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7 link	c.1683A>G	p.Leu561Leu	synonymous_variant	Exon 5 of 53	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61531

AN:

151868

Hom.:

13166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.0626

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.394

GnomAD2 exomes

AF:

0.345

AC:

86525

AN:

250826

AF XY:

0.339

show subpopulations

Gnomad AFR exome

AF:

0.502

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.0588

Gnomad FIN exome

AF:

0.435

Gnomad NFE exome

AF:

0.406

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.382

AC:

559037

AN:

1461688

Hom.:

111243

Cov.:

AF XY:

0.377

AC XY:

274214

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.500

AC:

16733

AN:

33472

American (AMR)

AF:

0.285

AC:

12732

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

9555

AN:

26134

East Asian (EAS)

AF:

0.0858

AC:

3403

AN:

39678

South Asian (SAS)

AF:

0.210

AC:

18132

AN:

86256

European-Finnish (FIN)

AF:

0.435

AC:

23215

AN:

53418

Middle Eastern (MID)

AF:

0.326

AC:

1879

AN:

5768

European-Non Finnish (NFE)

AF:

0.406

AC:

451246

AN:

1111860

Other (OTH)

AF:

0.367

AC:

22142

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

21307

42614

63920

85227

106534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.405

AC:

61593

AN:

151986

Hom.:

13180

Cov.:

AF XY:

0.398

AC XY:

29563

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.495

AC:

20497

AN:

41434

American (AMR)

AF:

0.327

AC:

5003

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1247

AN:

3470

East Asian (EAS)

AF:

0.0628

AC:

325

AN:

5176

South Asian (SAS)

AF:

0.194

AC:

935

AN:

4816

European-Finnish (FIN)

AF:

0.432

AC:

4552

AN:

10526

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27743

AN:

67974

Other (OTH)

AF:

0.391

AC:

824

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1837

3675

5512

7350

9187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.402

Hom.:

19302

Bravo

AF:

0.402

Asia WGS

AF:

0.156

AC:

546

AN:

3478

EpiCase

AF:

0.392

EpiControl

AF:

0.400

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 50% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:2Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Jun 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Chédiak-Higashi syndrome

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.47

(source)

DANN

Benign

0.48

PhyloP100

-0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs3820553

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over