chr1-235663082-TA-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000081.4(LYST):c.11268-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 24874 hom., cov: 0)

Exomes 𝑓: 0.45 ( 44544 hom. )

Failed GnomAD Quality Control

Consequence

LYST
NM_000081.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13O:1

Conservation

PhyloP100: -0.694

Publications

6 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 -16 ACMG points.

BP6

Variant 1-235663082-TA-T is Benign according to our data. Variant chr1-235663082-TA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 403065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.11268-5delT		splice_region_variant, intron_variant	Intron 52 of 52	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.11268-5delT		splice_region_variant, intron_variant	Intron 52 of 52	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

82566

AN:

149220

Hom.:

24831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.773

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.487

Gnomad EAS

AF:

0.0495

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.526

Gnomad OTH

AF:

0.525

GnomAD2 exomes

AF:

0.508

AC:

82886

AN:

163066

AF XY:

0.508

show subpopulations

Gnomad AFR exome

AF:

0.681

Gnomad AMR exome

AF:

0.448

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.239

Gnomad FIN exome

AF:

0.530

Gnomad NFE exome

AF:

0.534

Gnomad OTH exome

AF:

0.512

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.451

AC:

505703

AN:

1122018

Hom.:

44544

Cov.:

AF XY:

0.451

AC XY:

251328

AN XY:

557718

show subpopulations

African (AFR)

AF:

0.582

AC:

14906

AN:

25598

American (AMR)

AF:

0.389

AC:

12497

AN:

32128

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

9746

AN:

20776

East Asian (EAS)

AF:

0.190

AC:

4370

AN:

22946

South Asian (SAS)

AF:

0.315

AC:

17610

AN:

55940

European-Finnish (FIN)

AF:

0.504

AC:

22250

AN:

44118

Middle Eastern (MID)

AF:

0.448

AC:

2031

AN:

4536

European-Non Finnish (NFE)

AF:

0.462

AC:

400966

AN:

868486

Other (OTH)

AF:

0.449

AC:

21327

AN:

47490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

13920

27840

41759

55679

69599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13180

26360

39540

52720

65900

<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:

0.554

AC:

82650

AN:

149304

Hom.:

24874

Cov.:

AF XY:

0.540

AC XY:

39239

AN XY:

72718

show subpopulations

African (AFR)

AF:

0.774

AC:

31731

AN:

41020

American (AMR)

AF:

0.390

AC:

5786

AN:

14854

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

1667

AN:

3426

East Asian (EAS)

AF:

0.0497

AC:

251

AN:

5054

South Asian (SAS)

AF:

0.176

AC:

822

AN:

4678

European-Finnish (FIN)

AF:

0.549

AC:

5432

AN:

9898

Middle Eastern (MID)

AF:

0.504

AC:

141

AN:

280

European-Non Finnish (NFE)

AF:

0.526

AC:

35295

AN:

67112

Other (OTH)

AF:

0.522

AC:

1085

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1623

3246

4868

6491

8114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.430

Hom.:

1207

Bravo

AF:

0.553

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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 44% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. 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: Frequency -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Chédiak-Higashi syndrome

Benign:5

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

African/African American population allele frequency is 66.84% (rs767372373, 14,577/20,186 alleles, 4,812 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.1.0, this variant is classified as BENIGN. Following criteria are met: BA1 -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

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

- -

Jun 11, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 22, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27781387, 29357941) -

Autoinflammatory syndrome

Benign:1

Dec 01, 2019

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

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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