rs7543060

Variant names:

• chr1-235781098-A-C
• rs7543060
• NM_000081.4:c.5024-43T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-235781098-A-C
• chr1-235781098-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000081.4(LYST):​c.5024-43T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00877 in 1,243,592 control chromosomes in the GnomAD database, including 684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (416 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (268 hom.)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.689
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 1-235781098-A-C is Benign according to our data. Variant chr1-235781098-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 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.5024-43T>G		intron	N/A	NP_000072.2
	LYST	NM_001301365.1		c.5024-43T>G		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.5024-43T>G		intron	N/A	ENSP00000374443.2
	LYST	ENST00000489585.5	TSL:1	n.5024-43T>G		intron	N/A	ENSP00000513166.1
	LYST	ENST00000697178.1		n.*448-43T>G		intron	N/A	ENSP00000513163.1

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6049 AN: 152038 Hom.: 415 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0106 AC: 2190 AN: 205782 AF XY: 0.00818

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.00688

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000548

Gnomad OTH exome AF: 0.00645

GnomAD4 exome AF: 0.00443 AC: 4833 AN: 1091436 Hom.: 268 Cov.: 14 AF XY: 0.00372 AC XY: 2072 AN XY: 556626

African (AFR) AF: 0.139 AC: 3661 AN: 26282

American (AMR) AF: 0.00794 AC: 321 AN: 40418

Ashkenazi Jewish (ASJ) AF: 0.0000428 AC: 1 AN: 23376

East Asian (EAS) AF: 0.0000268 AC: 1 AN: 37314

South Asian (SAS) AF: 0.000305 AC: 23 AN: 75410

European-Finnish (FIN) AF: 0.0000582 AC: 3 AN: 51508

Middle Eastern (MID) AF: 0.00725 AC: 29 AN: 4002

European-Non Finnish (NFE) AF: 0.000325 AC: 255 AN: 785432

Other (OTH) AF: 0.0113 AC: 539 AN: 47694

GnomAD4 genome AF: 0.0399 AC: 6069 AN: 152156 Hom.: 416 Cov.: 32 AF XY: 0.0380 AC XY: 2830 AN XY: 74416

African (AFR) AF: 0.139 AC: 5749 AN: 41468

American (AMR) AF: 0.0149 AC: 228 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68004

Other (OTH) AF: 0.0242 AC: 51 AN: 2110

Alfa AF: 0.0158 Hom.: 58

Bravo AF: 0.0464

Asia WGS AF: 0.0130 AC: 44 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		-0.69
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: rs7543060; hg19: chr1-235944398;