Variant 1-235697040-C-T 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.10564+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,571,076 control chromosomes in the GnomAD database, including 195,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23488 hom., cov: 32)

Exomes 𝑓: 0.48 ( 172068 hom. )

Consequence

LYST
NM_000081.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.88

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=-0.93).

BP6

Variant 1-235697040-C-T is Benign according to our data. Variant chr1-235697040-C-T is described in ClinVar as [Benign]. Clinvar id is 254908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 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.10564+43G>A		intron_variant		ENST00000389793.7	NP_000072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7 linkuse as main transcript	c.10564+43G>A		intron_variant		5	NM_000081.4	ENSP00000374443	P1	Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80881

AN:

152004

Hom.:

23439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.0451

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.509

GnomAD3 exomes

AF:

0.420

AC:

103367

AN:

245900

Hom.:

25505

AF XY:

0.412

AC XY:

54796

AN XY:

132914

show subpopulations

Gnomad AFR exome

AF:

0.731

Gnomad AMR exome

AF:

0.273

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.0498

Gnomad SAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.535

Gnomad NFE exome

AF:

0.515

Gnomad OTH exome

AF:

0.459

GnomAD4 exome

AF:

0.477

AC:

676800

AN:

1418954

Hom.:

172068

Cov.:

AF XY:

0.468

AC XY:

331761

AN XY:

708282

show subpopulations

Gnomad4 AFR exome

AF:

0.726

Gnomad4 AMR exome

AF:

0.286

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.0509

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.540

Gnomad4 NFE exome

AF:

0.513

Gnomad4 OTH exome

AF:

0.464

GnomAD4 genome

AF:

0.532

AC:

80978

AN:

152122

Hom.:

23488

Cov.:

AF XY:

0.519

AC XY:

38594

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.722

Gnomad4 AMR

AF:

0.381

Gnomad4 ASJ

AF:

0.489

Gnomad4 EAS

AF:

0.0452

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.534

Gnomad4 NFE

AF:

0.517

Gnomad4 OTH

AF:

0.506

Alfa

AF:

0.523

Hom.:

4490

Bravo

AF:

0.532

Asia WGS

AF:

0.161

AC:

563

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.055

DANN

Benign

0.79

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