rs3768056

Variant names:

• chr1-235744525-G-A
• rs3768056
• NM_000081.4:c.7973-368C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-235744525-G-A
• chr1-235744525-G-C
• chr1-235744525-G-T

Variant summary

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

The NM_000081.4(LYST):​c.7973-368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,062 control chromosomes in the GnomAD database, including 49,027 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 0.80 (49027 hom., cov: 31)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.614
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4	c.7973-368C>T		intron_variant	Intron 29 of 52	ENST00000389793.7	NP_000072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7	c.7973-368C>T		intron_variant	Intron 29 of 52	5	NM_000081.4	ENSP00000374443.2

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121655 AN: 151944 Hom.: 48963 Cov.: 31

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.836

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.801 AC: 121779 AN: 152062 Hom.: 49027 Cov.: 31 AF XY: 0.802 AC XY: 59633 AN XY: 74322

African (AFR) AF: 0.898 AC: 37234 AN: 41478

American (AMR) AF: 0.748 AC: 11430 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2577 AN: 3466

East Asian (EAS) AF: 0.836 AC: 4333 AN: 5184

South Asian (SAS) AF: 0.771 AC: 3715 AN: 4820

European-Finnish (FIN) AF: 0.802 AC: 8448 AN: 10534

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51402 AN: 67988

Other (OTH) AF: 0.795 AC: 1678 AN: 2110

Alfa AF: 0.757 Hom.: 21554

Bravo AF: 0.801

Asia WGS AF: 0.798 AC: 2771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.94
DANN	Benign	0.27
PhyloP100		0.61
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: rs3768056; hg19: chr1-235907825;