rs7535375

chr1-235749859-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000081.4(LYST):c.7780+1351G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,898 control chromosomes in the GnomAD database, including 22,333 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 0.50 (22333 hom., cov: 31)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYST	NM_000081.4	c.7780+1351G>A		intron_variant		ENST00000389793.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYST	ENST00000389793.7	c.7780+1351G>A		intron_variant		5	NM_000081.4	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75697 AN: 151778 Hom.: 22282 Cov.: 31

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.0618

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.499 AC: 75806 AN: 151898 Hom.: 22333 Cov.: 31 AF XY: 0.488 AC XY: 36245 AN XY: 74240

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.0619

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.452

Alfa AF: 0.419 Hom.: 7580

Bravo AF: 0.509

Asia WGS AF: 0.181 AC: 631 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	0.18
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs7535375; hg19: chr1-235913159; COSMIC: COSV67705019;