NM_000081.4:c.10564+43G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000081.4(LYST):c.10564+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,571,076 control chromosomes in the GnomAD database, including 195,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23488 hom., cov: 32)

Exomes 𝑓: 0.48 ( 172068 hom. )

Consequence

LYST
NM_000081.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.88

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:

ENSG00000296841 (HGNC:):

ENSG00000296841 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-235697040-C-T is Benign according to our data. Variant chr1-235697040-C-T is described in ClinVar as Benign. ClinVar VariationId is 254908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.10564+43G>A		intron_variant	Intron 46 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.10564+43G>A		intron_variant	Intron 46 of 52	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80881

AN:

152004

Hom.:

23439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.0451

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.509

GnomAD2 exomes

AF:

0.420

AC:

103367

AN:

245900

AF XY:

0.412

show subpopulations

Gnomad AFR exome

AF:

0.731

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.0498

Gnomad FIN exome

AF:

0.535

Gnomad NFE exome

AF:

0.515

Gnomad OTH exome

AF:

0.459

GnomAD4 exome

AF:

0.477

AC:

676800

AN:

1418954

Hom.:

172068

Cov.:

AF XY:

0.468

AC XY:

331761

AN XY:

708282

show subpopulations

African (AFR)

AF:

0.726

AC:

23728

AN:

32692

American (AMR)

AF:

0.286

AC:

12676

AN:

44272

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

12778

AN:

25826

East Asian (EAS)

AF:

0.0509

AC:

2006

AN:

39422

South Asian (SAS)

AF:

0.189

AC:

16037

AN:

84886

European-Finnish (FIN)

AF:

0.540

AC:

28758

AN:

53240

Middle Eastern (MID)

AF:

0.456

AC:

2574

AN:

5646

European-Non Finnish (NFE)

AF:

0.513

AC:

550912

AN:

1074010

Other (OTH)

AF:

0.464

AC:

27331

AN:

58960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

16618

33236

49853

66471

83089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15352

30704

46056

61408

76760

<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:

0.532

AC:

80978

AN:

152122

Hom.:

23488

Cov.:

AF XY:

0.519

AC XY:

38594

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.722

AC:

29967

AN:

41498

American (AMR)

AF:

0.381

AC:

5814

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.489

AC:

1696

AN:

3470

East Asian (EAS)

AF:

0.0452

AC:

234

AN:

5180

South Asian (SAS)

AF:

0.171

AC:

823

AN:

4822

European-Finnish (FIN)

AF:

0.534

AC:

5655

AN:

10580

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.517

AC:

35139

AN:

67976

Other (OTH)

AF:

0.506

AC:

1068

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1813

3626

5438

7251

9064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.523

Hom.:

4490

Bravo

AF:

0.532

Asia WGS

AF:

0.161

AC:

563

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.055

(source)

DANN

Benign

0.79

PhyloP100

-1.9

Mutation Taster

=24/76

disease causing

(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