dbSNP rs141197189: LYST:c.5923-19G>T (chr1-235766296-C-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000081.4(LYST):c.5923-19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,561,406 control chromosomes in the GnomAD database, including 1,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 99 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1669 hom. )

Consequence

LYST
NM_000081.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0930

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 1-235766296-C-A is Benign according to our data. Variant chr1-235766296-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 254930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.5923-19G>T		intron_variant	Intron 20 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.5923-19G>T		intron_variant	Intron 20 of 52	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.0305

AC:

4639

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00978

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0406

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0474

Gnomad OTH

AF:

0.0302

GnomAD3 exomes

AF:

0.0306

AC:

6986

AN:

228040

Hom.:

136

AF XY:

0.0313

AC XY:

3890

AN XY:

124422

show subpopulations

Gnomad AFR exome

AF:

0.00755

Gnomad AMR exome

AF:

0.0344

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0243

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.0437

Gnomad OTH exome

AF:

0.0283

GnomAD4 exome

AF:

0.0442

AC:

62349

AN:

1409264

Hom.:

1669

Cov.:

AF XY:

0.0434

AC XY:

30477

AN XY:

702872

show subpopulations

Gnomad4 AFR exome

AF:

0.00819

Gnomad4 AMR exome

AF:

0.0343

Gnomad4 ASJ exome

AF:

0.0181

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.0266

Gnomad4 FIN exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.0510

Gnomad4 OTH exome

AF:

0.0381

GnomAD4 genome

AF:

0.0305

AC:

4640

AN:

152142

Hom.:

Cov.:

AF XY:

0.0290

AC XY:

2156

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00975

Gnomad4 AMR

AF:

0.0406

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0228

Gnomad4 FIN

AF:

0.0143

Gnomad4 NFE

AF:

0.0474

Gnomad4 OTH

AF:

0.0299

Alfa

AF:

0.0192

Hom.:

Bravo

AF:

0.0323

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 12, 2019

GeneDx

Significance: Likely 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

- -

Chédiak-Higashi syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.42

CADD

Benign

DANN

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over