rs11583387

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.4392C>T(p.Asn1464Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,614,028 control chromosomes in the GnomAD database, including 9,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 710 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8917 hom. )

Consequence

LYST
NM_000081.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.08

Publications

13 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=-0.49).

BP6

Variant 1-235791850-G-A is Benign according to our data. Variant chr1-235791850-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.4392C>T	p.Asn1464Asn	synonymous_variant	Exon 12 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.4392C>T	p.Asn1464Asn	synonymous_variant	Exon 12 of 53	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.0908

AC:

13809

AN:

152134

Hom.:

711

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0642

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.0921

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.0433

Gnomad SAS

AF:

0.0314

Gnomad FIN

AF:

0.0873

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.107

GnomAD2 exomes

AF:

0.0882

AC:

22154

AN:

251212

AF XY:

0.0876

show subpopulations

Gnomad AFR exome

AF:

0.0660

Gnomad AMR exome

AF:

0.0778

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.0827

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.107

AC:

156298

AN:

1461776

Hom.:

8917

Cov.:

AF XY:

0.105

AC XY:

76584

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.0641

AC:

2147

AN:

33480

American (AMR)

AF:

0.0800

AC:

3577

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

2860

AN:

26136

East Asian (EAS)

AF:

0.0493

AC:

1956

AN:

39694

South Asian (SAS)

AF:

0.0388

AC:

3344

AN:

86256

European-Finnish (FIN)

AF:

0.0860

AC:

4594

AN:

53420

Middle Eastern (MID)

AF:

0.136

AC:

784

AN:

5768

European-Non Finnish (NFE)

AF:

0.118

AC:

130769

AN:

1111906

Other (OTH)

AF:

0.104

AC:

6267

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

8320

16639

24959

33278

41598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4692

9384

14076

18768

23460

<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:

0.0907

AC:

13807

AN:

152252

Hom.:

710

Cov.:

AF XY:

0.0882

AC XY:

6570

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0641

AC:

2663

AN:

41538

American (AMR)

AF:

0.0919

AC:

1406

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

390

AN:

3470

East Asian (EAS)

AF:

0.0434

AC:

225

AN:

5190

South Asian (SAS)

AF:

0.0306

AC:

148

AN:

4830

European-Finnish (FIN)

AF:

0.0873

AC:

926

AN:

10602

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.113

AC:

7672

AN:

67996

Other (OTH)

AF:

0.105

AC:

223

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

642

1283

1925

2566

3208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.104

Hom.:

567

Bravo

AF:

0.0921

Asia WGS

AF:

0.0390

AC:

136

AN:

3478

EpiCase

AF:

0.120

EpiControl

AF:

0.121

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Chédiak-Higashi syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Oct 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.49

CADD

Benign

8.7

(source)

DANN

Benign

0.67

PhyloP100

3.1

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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