rs6696123

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.4956A>G(p.Leu1652Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,611,766 control chromosomes in the GnomAD database, including 124,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13168 hom., cov: 31)

Exomes 𝑓: 0.38 ( 111053 hom. )

Consequence

LYST
NM_000081.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.385

Publications

19 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 1-235781994-T-C is Benign according to our data. Variant chr1-235781994-T-C is described in ClinVar as Benign. ClinVar VariationId is 254923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.385 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.4956A>G	p.Leu1652Leu	synonymous_variant	Exon 15 of 53	ENST00000389793.7	NP_000072.2	Q99698-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LYST	ENST00000389793.7 link	c.4956A>G	p.Leu1652Leu	synonymous_variant	Exon 15 of 53	5	NM_000081.4	ENSP00000374443.2	Q99698-1
LYST	ENST00000489585.5 link	n.4956A>G		non_coding_transcript_exon_variant	Exon 15 of 23	1		ENSP00000513166.1	Q99698-2
LYST	ENST00000697178.1 link	n.*380A>G		non_coding_transcript_exon_variant	Exon 14 of 52			ENSP00000513163.1	A0A8V8TKT6
LYST	ENST00000697178.1 link	n.*380A>G		3_prime_UTR_variant	Exon 14 of 52			ENSP00000513163.1	A0A8V8TKT6

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61498

AN:

151856

Hom.:

13154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.494

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.326

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.0631

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.392

GnomAD2 exomes

AF:

0.345

AC:

86470

AN:

250828

AF XY:

0.339

show subpopulations

Gnomad AFR exome

AF:

0.502

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.367

Gnomad EAS exome

AF:

0.0588

Gnomad FIN exome

AF:

0.435

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.382

AC:

557670

AN:

1459794

Hom.:

111053

Cov.:

AF XY:

0.377

AC XY:

273600

AN XY:

726288

show subpopulations

African (AFR)

AF:

0.500

AC:

16705

AN:

33432

American (AMR)

AF:

0.284

AC:

12699

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

9606

AN:

26130

East Asian (EAS)

AF:

0.0856

AC:

3395

AN:

39640

South Asian (SAS)

AF:

0.210

AC:

18106

AN:

86218

European-Finnish (FIN)

AF:

0.434

AC:

23181

AN:

53370

Middle Eastern (MID)

AF:

0.325

AC:

1869

AN:

5758

European-Non Finnish (NFE)

AF:

0.405

AC:

450023

AN:

1110214

Other (OTH)

AF:

0.366

AC:

22086

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

15872

31743

47615

63486

79358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13646

27292

40938

54584

68230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.405

AC:

61559

AN:

151972

Hom.:

13168

Cov.:

AF XY:

0.398

AC XY:

29552

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.495

AC:

20491

AN:

41436

American (AMR)

AF:

0.326

AC:

4978

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1254

AN:

3468

East Asian (EAS)

AF:

0.0632

AC:

327

AN:

5172

South Asian (SAS)

AF:

0.195

AC:

942

AN:

4828

European-Finnish (FIN)

AF:

0.433

AC:

4558

AN:

10520

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27720

AN:

67964

Other (OTH)

AF:

0.389

AC:

821

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1818

3636

5453

7271

9089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.402

Hom.:

42720

Bravo

AF:

0.401

Asia WGS

AF:

0.156

AC:

544

AN:

3478

EpiCase

AF:

0.391

EpiControl

AF:

0.399

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

2.6

(source)

DANN

Benign

0.67

PhyloP100

-0.39

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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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