1-235677195-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000081.4(LYST):c.10941-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00824 in 1,587,792 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0063 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 83 hom. )

Consequence

LYST
NM_000081.4 splice_region, intron

Scores

Splicing: ADA: 0.0003070

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:9

Conservation

PhyloP100: 0.494

Publications

1 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:

ENSG00000296841 (HGNC:):

ENSG00000296841 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 1-235677195-G-T is Benign according to our data. Variant chr1-235677195-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 235367.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00626 (951/152036) while in subpopulation SAS AF = 0.0104 (50/4814). AF 95% confidence interval is 0.0092. There are 4 homozygotes in GnomAd4. There are 456 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000081.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	NM_000081.4	MANE Select	c.10941-7C>A		splice_region intron	N/A	NP_000072.2
	LYST	NM_001301365.1		c.10941-7C>A		splice_region intron	N/A	NP_001288294.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LYST	ENST00000389793.7	TSL:5 MANE Select	c.10941-7C>A	splice_region intron	N/A	ENSP00000374443.2
LYST	ENST00000697178.1		n.*6920C>A	non_coding_transcript_exon	Exon 49 of 52	ENSP00000513163.1
LYST	ENST00000697178.1		n.*6920C>A	3_prime_UTR	Exon 49 of 52	ENSP00000513163.1

Frequencies

GnomAD3 genomes

AF:

0.00626

AC:

951

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.00761

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00981

Gnomad OTH

AF:

0.00622

GnomAD2 exomes

AF:

0.00699

AC:

1753

AN:

250680

AF XY:

0.00759

show subpopulations

Gnomad AFR exome

AF:

0.000986

Gnomad AMR exome

AF:

0.00318

Gnomad ASJ exome

AF:

0.00716

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00906

Gnomad NFE exome

AF:

0.00858

Gnomad OTH exome

AF:

0.00720

GnomAD4 exome

AF:

0.00845

AC:

12137

AN:

1435756

Hom.:

Cov.:

AF XY:

0.00869

AC XY:

6220

AN XY:

715820

show subpopulations

African (AFR)

AF:

0.000850

AC:

AN:

32938

American (AMR)

AF:

0.00311

AC:

139

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00721

AC:

187

AN:

25938

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39584

South Asian (SAS)

AF:

0.0115

AC:

986

AN:

85720

European-Finnish (FIN)

AF:

0.00873

AC:

466

AN:

53380

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00900

AC:

9791

AN:

1088280

Other (OTH)

AF:

0.00781

AC:

465

AN:

59530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

600

1199

1799

2398

2998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.00626

AC:

951

AN:

152036

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

456

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41502

American (AMR)

AF:

0.00406

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.0104

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00761

AC:

AN:

10518

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00981

AC:

667

AN:

67966

Other (OTH)

AF:

0.00616

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

101

151

202

252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00698

Hom.:

Bravo

AF:

0.00559

EpiCase

AF:

0.0101

EpiControl

AF:

0.00919

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:9

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Chédiak-Higashi syndrome

Uncertain:1Benign:3

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 02, 2016

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

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

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:4

Mar 18, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LYST: BP4, BS1, BS2

Apr 03, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Autoinflammatory syndrome

Benign:1

Jan 24, 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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.5

(source)

DANN

Benign

0.72

PhyloP100

0.49

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00031

dbscSNV1_RF

Benign

0.034

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over