rs3768051

Variant names:

• chr1-235696414-G-T
• rs3768051
• NM_000081.4:c.10564+669C>A

Variant summary

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

The NM_000081.4(LYST):​c.10564+669C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 152,274 control chromosomes in the GnomAD database, including 509 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 0.077 (509 hom., cov: 32)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 5 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

ENSG00000296841 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.0883 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.10564+669C>A		intron	N/A	NP_000072.2
	LYST	NM_001301365.1		c.10564+669C>A		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.10564+669C>A		intron	N/A	ENSP00000374443.2
	LYST	ENST00000697179.1		n.3942C>A		non_coding_transcript_exon	Exon 4 of 4
	LYST	ENST00000697235.1		c.1114+669C>A		intron	N/A	ENSP00000513202.1

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11748 AN: 152156 Hom.: 510 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0902

Gnomad OTH AF: 0.0910

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

GnomAD4 genome AF: 0.0771 AC: 11745 AN: 152274 Hom.: 509 Cov.: 32 AF XY: 0.0748 AC XY: 5569 AN XY: 74444

African (AFR) AF: 0.0613 AC: 2548 AN: 41554

American (AMR) AF: 0.0861 AC: 1316 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3470

East Asian (EAS) AF: 0.0432 AC: 224 AN: 5190

South Asian (SAS) AF: 0.0319 AC: 154 AN: 4826

European-Finnish (FIN) AF: 0.0611 AC: 648 AN: 10610

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0902 AC: 6133 AN: 68016

Other (OTH) AF: 0.0896 AC: 189 AN: 2110

Alfa AF: 0.0853 Hom.: 412

Bravo AF: 0.0807

Asia WGS AF: 0.0380 AC: 132 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	0.0020
DANN	Benign	0.58
PhyloP100		-1.9
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: rs3768051; hg19: chr1-235859714; COSMIC: COSV67704846;