rs11583387

chr1-235791850-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000081.4(LYST):c.4392C>T(p.Asn1464=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,614,028 control chromosomes in the GnomAD database, including 9,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (710 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8917 hom.)
• Consequence: LYST NM_000081.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.08

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 1-235791850-G-A is Benign according to our data. Variant chr1-235791850-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 254921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYST	NM_000081.4	c.4392C>T	p.Asn1464=	synonymous_variant	12/53	ENST00000389793.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYST	ENST00000389793.7	c.4392C>T	p.Asn1464=	synonymous_variant	12/53	5	NM_000081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0908 AC: 13809 AN: 152134 Hom.: 711 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0433

Gnomad SAS AF: 0.0314

Gnomad FIN AF: 0.0873

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.0882 AC: 22154 AN: 251212 Hom.: 1092 AF XY: 0.0876 AC XY: 11887 AN XY: 135746

Gnomad AFR exome AF: 0.0660

Gnomad AMR exome AF: 0.0778

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.0491

Gnomad SAS exome AF: 0.0381

Gnomad FIN exome AF: 0.0827

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.107 AC: 156298 AN: 1461776 Hom.: 8917 Cov.: 32 AF XY: 0.105 AC XY: 76584 AN XY: 727202

Gnomad4 AFR exome AF: 0.0641

Gnomad4 AMR exome AF: 0.0800

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0493

Gnomad4 SAS exome AF: 0.0388

Gnomad4 FIN exome AF: 0.0860

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.0907 AC: 13807 AN: 152252 Hom.: 710 Cov.: 32 AF XY: 0.0882 AC XY: 6570 AN XY: 74450

Gnomad4 AFR AF: 0.0641

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0434

Gnomad4 SAS AF: 0.0306

Gnomad4 FIN AF: 0.0873

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.105

Alfa AF: 0.104 Hom.: 450

Bravo AF: 0.0921

Asia WGS AF: 0.0390 AC: 136 AN: 3478

EpiCase AF: 0.120

EpiControl AF: 0.121

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	8.7
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs11583387; hg19: chr1-235955150;