Variant rs17615059 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000081.4(LYST):c.10374+33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,562,692 control chromosomes in the GnomAD database, including 808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 46 hom., cov: 32)

Exomes 𝑓: 0.030 ( 762 hom. )

Consequence

LYST
NM_000081.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.462

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=-0.66).

BP6

Variant 1-235702714-T-C is Benign according to our data. Variant chr1-235702714-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 254907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-235702714-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0217 (3305/152270) while in subpopulation NFE AF= 0.0339 (2303/68014). AF 95% confidence interval is 0.0327. There are 46 homozygotes in gnomad4. There are 1511 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.10374+33A>G		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 link	c.10374+33A>G		intron_variant		5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3310

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00615

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00809

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0339

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0227

AC:

5684

AN:

250188

Hom.:

AF XY:

0.0237

AC XY:

3213

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.00492

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.0444

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.0185

Gnomad NFE exome

AF:

0.0341

Gnomad OTH exome

AF:

0.0296

GnomAD4 exome

AF:

0.0305

AC:

42962

AN:

1410422

Hom.:

762

Cov.:

AF XY:

0.0297

AC XY:

20951

AN XY:

704894

show subpopulations

Gnomad4 AFR exome

AF:

0.00514

Gnomad4 AMR exome

AF:

0.0125

Gnomad4 ASJ exome

AF:

0.0448

Gnomad4 EAS exome

AF:

0.0000761

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.0212

Gnomad4 NFE exome

AF:

0.0349

Gnomad4 OTH exome

AF:

0.0290

GnomAD4 genome

AF:

0.0217

AC:

3305

AN:

152270

Hom.:

Cov.:

AF XY:

0.0203

AC XY:

1511

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00614

Gnomad4 AMR

AF:

0.0188

Gnomad4 ASJ

AF:

0.0484

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00789

Gnomad4 FIN

AF:

0.0162

Gnomad4 NFE

AF:

0.0339

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0210

Asia WGS

AF:

0.00462

AC:

AN:

3478

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	clinical testing	GeneDx	Aug 28, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.9

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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