chr1-235808463-A-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.2355T>C(p.Leu785Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,612,112 control chromosomes in the GnomAD database, including 13,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 973 hom., cov: 31)

Exomes 𝑓: 0.13 ( 12773 hom. )

Consequence

LYST
NM_000081.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0390

Publications

14 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=-0.76).

BP6

Variant 1-235808463-A-G is Benign according to our data. Variant chr1-235808463-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.039 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.2355T>C	p.Leu785Leu	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.2355T>C	p.Leu785Leu	synonymous_variant	Exon 5 of 53	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16255

AN:

151454

Hom.:

975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0710

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.0435

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.163

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.124

GnomAD2 exomes

AF:

0.105

AC:

26266

AN:

250712

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.0716

Gnomad AMR exome

AF:

0.0882

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.0494

Gnomad FIN exome

AF:

0.0965

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.128

AC:

186892

AN:

1460542

Hom.:

12773

Cov.:

AF XY:

0.126

AC XY:

91613

AN XY:

726448

show subpopulations

African (AFR)

AF:

0.0707

AC:

2366

AN:

33450

American (AMR)

AF:

0.0909

AC:

4055

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

3792

AN:

26096

East Asian (EAS)

AF:

0.0495

AC:

1965

AN:

39664

South Asian (SAS)

AF:

0.0420

AC:

3624

AN:

86206

European-Finnish (FIN)

AF:

0.100

AC:

5364

AN:

53382

Middle Eastern (MID)

AF:

0.165

AC:

949

AN:

5758

European-Non Finnish (NFE)

AF:

0.142

AC:

157311

AN:

1111026

Other (OTH)

AF:

0.124

AC:

7466

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

7714

15428

23142

30856

38570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5520

11040

16560

22080

27600

<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:

0.107

AC:

16251

AN:

151570

Hom.:

973

Cov.:

AF XY:

0.103

AC XY:

7629

AN XY:

74032

show subpopulations

African (AFR)

AF:

0.0709

AC:

2930

AN:

41324

American (AMR)

AF:

0.105

AC:

1600

AN:

15168

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

498

AN:

3462

East Asian (EAS)

AF:

0.0436

AC:

225

AN:

5158

South Asian (SAS)

AF:

0.0330

AC:

158

AN:

4792

European-Finnish (FIN)

AF:

0.100

AC:

1048

AN:

10478

Middle Eastern (MID)

AF:

0.172

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.138

AC:

9374

AN:

67886

Other (OTH)

AF:

0.122

AC:

257

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

700

1400

2099

2799

3499

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<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:

0.132

Hom.:

2527

Bravo

AF:

0.109

Asia WGS

AF:

0.0420

AC:

145

AN:

3476

EpiCase

AF:

0.150

EpiControl

AF:

0.148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2024

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 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

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

- -

not provided

Benign:2

Jun 25, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.7

(source)

DANN

Benign

0.71

PhyloP100

-0.039

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