chr1-235762863-AT-A

Variant names:

• chr1-235762863-AT-A
• rs201404906
• NM_000081.4:c.6122-13delA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000081.4(LYST):​c.6122-13delA variant causes a 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 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.482
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Chediak-Higashi syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• attenuated Chédiak-Higashi syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000081.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	NM_000081.4	MANE Select	c.6122-13delA		intron	N/A	NP_000072.2
	LYST	NM_001301365.1		c.6122-13delA		intron	N/A	NP_001288294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	ENST00000389793.7	TSL:5 MANE Select	c.6122-13delA		intron	N/A	ENSP00000374443.2
	LYST	ENST00000489585.5	TSL:1	n.5962-13delA		intron	N/A	ENSP00000513166.1
	LYST	ENST00000697241.1		c.554-13delA		intron	N/A	ENSP00000513206.1

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

GnomAD2 exomes AF: 0.00608 AC: 1503 AN: 247242 AF XY: 0.00448

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 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

African (AFR) AF: 0.0728 AC: 2428 AN: 33334

American (AMR) AF: 0.00489 AC: 218 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.0000768 AC: 2 AN: 26044

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39494

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86076

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53250

Middle Eastern (MID) AF: 0.00557 AC: 32 AN: 5746

European-Non Finnish (NFE) AF: 0.000289 AC: 321 AN: 1108822

Other (OTH) AF: 0.00573 AC: 345 AN: 60194

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

African (AFR) AF: 0.0756 AC: 3138 AN: 41488

American (AMR) AF: 0.00838 AC: 128 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 67952

Other (OTH) AF: 0.0123 AC: 26 AN: 2108

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Jul 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 24, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs201404906; hg19: chr1-235926163; COSMIC: COSV101088851;