chr1-235755570-T-G

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.7137A>C(p.Leu2379Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 1,613,120 control chromosomes in the GnomAD database, including 1,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 98 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1140 hom. )

Consequence

LYST
NM_000081.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: 0.458

Publications

7 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=-0.48).

BP6

Variant 1-235755570-T-G is Benign according to our data. Variant chr1-235755570-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.458 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.7137A>C	p.Leu2379Leu	synonymous_variant	Exon 25 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.7137A>C	p.Leu2379Leu	synonymous_variant	Exon 25 of 53	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4371

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00649

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0665

Gnomad ASJ

AF:

0.0254

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0236

Gnomad FIN

AF:

0.0311

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0361

Gnomad OTH

AF:

0.0268

GnomAD2 exomes

AF:

0.0345

AC:

8675

AN:

251358

AF XY:

0.0332

show subpopulations

Gnomad AFR exome

AF:

0.00615

Gnomad AMR exome

AF:

0.0798

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0330

Gnomad NFE exome

AF:

0.0337

Gnomad OTH exome

AF:

0.0289

GnomAD4 exome

AF:

0.0362

AC:

52860

AN:

1460852

Hom.:

1140

Cov.:

AF XY:

0.0357

AC XY:

25972

AN XY:

726852

show subpopulations

African (AFR)

AF:

0.00499

AC:

167

AN:

33470

American (AMR)

AF:

0.0775

AC:

3465

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0234

AC:

611

AN:

26122

East Asian (EAS)

AF:

0.000151

AC:

AN:

39678

South Asian (SAS)

AF:

0.0277

AC:

2385

AN:

86232

European-Finnish (FIN)

AF:

0.0337

AC:

1798

AN:

53410

Middle Eastern (MID)

AF:

0.0166

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0382

AC:

42466

AN:

1111090

Other (OTH)

AF:

0.0309

AC:

1866

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2417

4834

7251

9668

12085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1614

3228

4842

6456

8070

<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:

0.0287

AC:

4375

AN:

152268

Hom.:

Cov.:

AF XY:

0.0291

AC XY:

2167

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.00647

AC:

269

AN:

41578

American (AMR)

AF:

0.0665

AC:

1017

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0254

AC:

AN:

3468

East Asian (EAS)

AF:

0.00116

AC:

AN:

5184

South Asian (SAS)

AF:

0.0240

AC:

116

AN:

4828

European-Finnish (FIN)

AF:

0.0311

AC:

330

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0361

AC:

2454

AN:

68004

Other (OTH)

AF:

0.0265

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

204

408

612

816

1020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0258

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0319

EpiControl

AF:

0.0311

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 12, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

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: Frequency -

Chédiak-Higashi syndrome

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely 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

- -

Autoinflammatory syndrome

Benign:1

Mar 05, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

-0.48

CADD

Benign

5.3

(source)

DANN

Benign

0.74

PhyloP100

0.46

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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