rs141197189

Positions:

• chr1-235766296-C-A
• chr1-235766296-C-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000081.4(LYST):​c.5923-19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,561,406 control chromosomes in the GnomAD database, including 1,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (99 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1669 hom.)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0930

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 1-235766296-C-A is Benign according to our data. Variant chr1-235766296-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 254930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYST	NM_000081.4	c.5923-19G>T		intron_variant		ENST00000389793.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYST	ENST00000389793.7	c.5923-19G>T		intron_variant		5	NM_000081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4639 AN: 152024 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.00978

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0302

GnomAD3 exomes AF: 0.0306 AC: 6986 AN: 228040 Hom.: 136 AF XY: 0.0313 AC XY: 3890 AN XY: 124422

Gnomad AFR exome AF: 0.00755

Gnomad AMR exome AF: 0.0344

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0243

Gnomad FIN exome AF: 0.0148

Gnomad NFE exome AF: 0.0437

Gnomad OTH exome AF: 0.0283

GnomAD4 exome AF: 0.0442 AC: 62349 AN: 1409264 Hom.: 1669 Cov.: 26 AF XY: 0.0434 AC XY: 30477 AN XY: 702872

Gnomad4 AFR exome AF: 0.00819

Gnomad4 AMR exome AF: 0.0343

Gnomad4 ASJ exome AF: 0.0181

Gnomad4 EAS exome AF: 0.000203

Gnomad4 SAS exome AF: 0.0266

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.0510

Gnomad4 OTH exome AF: 0.0381

GnomAD4 genome AF: 0.0305 AC: 4640 AN: 152142 Hom.: 99 Cov.: 32 AF XY: 0.0290 AC XY: 2156 AN XY: 74378

Gnomad4 AFR AF: 0.00975

Gnomad4 AMR AF: 0.0406

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0474

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0192 Hom.: 9

Bravo AF: 0.0323

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Chédiak-Higashi syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.63

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: rs141197189; hg19: chr1-235929596;