Variant 1-235755570-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000081.4(LYST):c.7137A>C(p.Leu2379Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 1,613,120 control chromosomes in the GnomAD database, including 1,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 98 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1140 hom. )

Consequence

LYST
NM_000081.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: 0.458

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 1-235755570-T-G is Benign according to our data. Variant chr1-235755570-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 254938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-235755570-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.458 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0632 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.7137A>C	p.Leu2379Leu	synonymous_variant	25/53	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.7137A>C	p.Leu2379Leu	synonymous_variant	25/53	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4371

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00649

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0665

Gnomad ASJ

AF:

0.0254

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0236

Gnomad FIN

AF:

0.0311

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0361

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0345

AC:

8675

AN:

251358

Hom.:

235

AF XY:

0.0332

AC XY:

4515

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00615

Gnomad AMR exome

AF:

0.0798

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0277

Gnomad FIN exome

AF:

0.0330

Gnomad NFE exome

AF:

0.0337

Gnomad OTH exome

AF:

0.0289

GnomAD4 exome

AF:

0.0362

AC:

52860

AN:

1460852

Hom.:

1140

Cov.:

AF XY:

0.0357

AC XY:

25972

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.00499

Gnomad4 AMR exome

AF:

0.0775

Gnomad4 ASJ exome

AF:

0.0234

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0277

Gnomad4 FIN exome

AF:

0.0337

Gnomad4 NFE exome

AF:

0.0382

Gnomad4 OTH exome

AF:

0.0309

GnomAD4 genome

AF:

0.0287

AC:

4375

AN:

152268

Hom.:

Cov.:

AF XY:

0.0291

AC XY:

2167

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00647

Gnomad4 AMR

AF:

0.0665

Gnomad4 ASJ

AF:

0.0254

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0240

Gnomad4 FIN

AF:

0.0311

Gnomad4 NFE

AF:

0.0361

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0264

Hom.:

Bravo

AF:

0.0309

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0319

EpiControl

AF:

0.0311

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2019	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.3

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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