Variant 1-235781098-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000081.4(LYST):c.5024-43T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00877 in 1,243,592 control chromosomes in the GnomAD database, including 684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 416 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 268 hom. )

Consequence

LYST
NM_000081.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.689

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 1-235781098-A-C is Benign according to our data. Variant chr1-235781098-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 254925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYST	NM_000081.4 linkuse as main transcript	c.5024-43T>G		intron_variant		ENST00000389793.7	NP_000072.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7 linkuse as main transcript	c.5024-43T>G	intron_variant	5	NM_000081.4	ENSP00000374443	P1	Q99698-1
LYST	ENST00000489585.5 linkuse as main transcript	c.5024-43T>G	intron_variant, NMD_transcript_variant	1		ENSP00000513166		Q99698-2
LYST	ENST00000697178.1 linkuse as main transcript	c.*448-43T>G	intron_variant, NMD_transcript_variant			ENSP00000513163

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

6049

AN:

152038

Hom.:

415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0149

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0106

AC:

2190

AN:

205782

Hom.:

140

AF XY:

0.00818

AC XY:

909

AN XY:

111162

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.00688

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000152

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000548

Gnomad OTH exome

AF:

0.00645

GnomAD4 exome

AF:

0.00443

AC:

4833

AN:

1091436

Hom.:

268

Cov.:

AF XY:

0.00372

AC XY:

2072

AN XY:

556626

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.00794

Gnomad4 ASJ exome

AF:

0.0000428

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.000305

Gnomad4 FIN exome

AF:

0.0000582

Gnomad4 NFE exome

AF:

0.000325

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.0399

AC:

6069

AN:

152156

Hom.:

416

Cov.:

AF XY:

0.0380

AC XY:

2830

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.0149

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.0242

Alfa

AF:

0.0253

Hom.:

Bravo

AF:

0.0464

Asia WGS

AF:

0.0130

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.88

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