1-235876577-T-C

Variant names:

• chr1-235876577-T-C
• rs9782955
• ENST00000468107.5:c.-98+6610A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001301365.1(LYST):​c.-98+6610A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,260 control chromosomes in the GnomAD database, including 51,562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51562 hom., cov: 33)
• Consequence: LYST NM_001301365.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• Publications: 27 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp
• attenuated Chédiak-Higashi syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301365.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	NM_001301365.1		c.-98+6610A>G		intron	N/A	NP_001288294.1	Q99698-1
	LYST	NR_102436.3		n.527+6610A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	ENST00000468107.5	TSL:1	c.-98+6610A>G		intron	N/A	ENSP00000513172.1	A0A8V8TMC0
	LYST	ENST00000465349.5	TSL:1	n.454+6610A>G		intron	N/A
	LYST	ENST00000489585.5	TSL:1	n.-98+6610A>G		intron	N/A	ENSP00000513166.1	Q99698-2

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124587 AN: 152142 Hom.: 51506 Cov.: 33

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.819 AC: 124703 AN: 152260 Hom.: 51562 Cov.: 33 AF XY: 0.821 AC XY: 61093 AN XY: 74442

African (AFR) AF: 0.948 AC: 39412 AN: 41578

American (AMR) AF: 0.770 AC: 11770 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2549 AN: 3470

East Asian (EAS) AF: 0.882 AC: 4573 AN: 5184

South Asian (SAS) AF: 0.775 AC: 3737 AN: 4820

European-Finnish (FIN) AF: 0.810 AC: 8574 AN: 10588

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51433 AN: 68014

Other (OTH) AF: 0.806 AC: 1703 AN: 2114

Alfa AF: 0.770 Hom.: 75069

Bravo AF: 0.822

Asia WGS AF: 0.817 AC: 2838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.31
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9782955; hg19: chr1-236039877;