Variant chr1-235762863-AT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000081.4(LYST):c.6122-13del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,609,582 control chromosomes in the GnomAD database, including 229 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 122 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 107 hom. )

Consequence

LYST
NM_000081.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.482

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 -16 ACMG points.

BP6

Variant 1-235762863-AT-A is Benign according to our data. Variant chr1-235762863-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 235635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYST	NM_000081.4 linkuse as main transcript	c.6122-13del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000389793.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYST	ENST00000389793.7 linkuse as main transcript	c.6122-13del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_000081.4	P1	Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3320

AN:

151924

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0758

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00839

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.00608

AC:

1503

AN:

247242

Hom.:

AF XY:

0.00448

AC XY:

599

AN XY:

133648

show subpopulations

Gnomad AFR exome

AF:

0.0789

Gnomad AMR exome

AF:

0.00429

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000502

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.00232

AC:

3376

AN:

1457540

Hom.:

107

Cov.:

AF XY:

0.00203

AC XY:

1473

AN XY:

725222

show subpopulations

Gnomad4 AFR exome

AF:

0.0728

Gnomad4 AMR exome

AF:

0.00489

Gnomad4 ASJ exome

AF:

0.0000768

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000289

Gnomad4 OTH exome

AF:

0.00573

GnomAD4 genome

AF:

0.0219

AC:

3324

AN:

152042

Hom.:

122

Cov.:

AF XY:

0.0206

AC XY:

1529

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0756

Gnomad4 AMR

AF:

0.00838

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.00347

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Chédiak-Higashi syndrome

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 24, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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