Variant 1-235663082-TAAA-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000081.4(LYST):c.11268-6_11268-5delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,314,560 control chromosomes in the GnomAD database, including 22 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 14 hom., cov: 0)

Exomes 𝑓: 0.012 ( 8 hom. )

Consequence

LYST
NM_000081.4 splice_region, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.14

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:

LYST (HGNC:):

LYST links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-235663082-TAA-T is Benign according to our data. Variant chr1-235663082-TAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 296344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-235663082-TAA-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00552 (824/149400) while in subpopulation AFR AF= 0.0174 (715/41034). AF 95% confidence interval is 0.0164. There are 14 homozygotes in gnomad4. There are 406 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYST	NM_000081.4 linkuse as main transcript	c.11268-6_11268-5delTT		splice_region_variant, intron_variant		ENST00000389793.7	NP_000072.2	Q99698-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7 linkuse as main transcript	c.11268-6_11268-5delTT		splice_region_variant, intron_variant		5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

822

AN:

149314

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00477

Gnomad ASJ

AF:

0.000583

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.000909

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000268

Gnomad OTH

AF:

0.00388

GnomAD4 exome

AF:

0.0117

AC:

13682

AN:

1165160

Hom.:

AF XY:

0.0109

AC XY:

6373

AN XY:

585776

show subpopulations

Gnomad4 AFR exome

AF:

0.0506

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.00823

Gnomad4 EAS exome

AF:

0.000180

Gnomad4 SAS exome

AF:

0.000977

Gnomad4 FIN exome

AF:

0.00876

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0110

GnomAD4 genome

AF:

0.00552

AC:

824

AN:

149400

Hom.:

Cov.:

AF XY:

0.00558

AC XY:

406

AN XY:

72770

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.000583

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.000909

Gnomad4 NFE

AF:

0.000268

Gnomad4 OTH

AF:

0.00385

Alfa

AF:

0.0237

Hom.:

1207

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Chédiak-Higashi syndrome

Benign:2

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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