rs201404906

Positions:

• chr1-235762863-AT-A
• chr1-235762863-AT-ATT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000081.4(LYST):​c.6122-13del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,609,582 control chromosomes in the GnomAD database, including 229 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (122 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (107 hom.)
• Consequence: LYST NM_000081.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.482

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 -16 ACMG points.

• BP6: Variant 1-235762863-AT-A is Benign according to our data. Variant chr1-235762863-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 235635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYST	NM_000081.4	c.6122-13del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000389793.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYST	ENST00000389793.7	c.6122-13del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_000081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3320 AN: 151924 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00839

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0125

GnomAD3 exomes AF: 0.00608 AC: 1503 AN: 247242 Hom.: 56 AF XY: 0.00448 AC XY: 599 AN XY: 133648

Gnomad AFR exome AF: 0.0789

Gnomad AMR exome AF: 0.00429

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.0000334

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000502

Gnomad OTH exome AF: 0.00397

GnomAD4 exome AF: 0.00232 AC: 3376 AN: 1457540 Hom.: 107 Cov.: 30 AF XY: 0.00203 AC XY: 1473 AN XY: 725222

Gnomad4 AFR exome AF: 0.0728

Gnomad4 AMR exome AF: 0.00489

Gnomad4 ASJ exome AF: 0.0000768

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000289

Gnomad4 OTH exome AF: 0.00573

GnomAD4 genome AF: 0.0219 AC: 3324 AN: 152042 Hom.: 122 Cov.: 32 AF XY: 0.0206 AC XY: 1529 AN XY: 74318

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.00838

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00132 Hom.: 1

Bravo AF: 0.0258

Asia WGS AF: 0.00347 AC: 12 AN: 3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

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	Jan 31, 2024	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 24, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

Computational scores

Source: dbNSFP v4.3

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: rs201404906; hg19: chr1-235926163;