rs7541057

chr1-235697040-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000081.4(LYST):c.10564+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,571,076 control chromosomes in the GnomAD database, including 195,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (23488 hom., cov: 32)
  • Exomes 𝑓: 0.48 (172068 hom.)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.88

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-235697040-C-T is Benign according to our data. Variant chr1-235697040-C-T is described in ClinVar as [Benign]. Clinvar id is 254908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYST	NM_000081.4	c.10564+43G>A		intron_variant		ENST00000389793.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYST	ENST00000389793.7	c.10564+43G>A		intron_variant		5	NM_000081.4	P1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80881 AN: 152004 Hom.: 23439 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.509

GnomAD3 exomes AF: 0.420 AC: 103367 AN: 245900 Hom.: 25505 AF XY: 0.412 AC XY: 54796 AN XY: 132914

Gnomad AFR exome AF: 0.731

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.0498

Gnomad SAS exome AF: 0.186

Gnomad FIN exome AF: 0.535

Gnomad NFE exome AF: 0.515

Gnomad OTH exome AF: 0.459

GnomAD4 exome AF: 0.477 AC: 676800 AN: 1418954 Hom.: 172068 Cov.: 23 AF XY: 0.468 AC XY: 331761 AN XY: 708282

Gnomad4 AFR exome AF: 0.726

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.0509

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.540

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.464

GnomAD4 genome AF: 0.532 AC: 80978 AN: 152122 Hom.: 23488 Cov.: 32 AF XY: 0.519 AC XY: 38594 AN XY: 74356

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.0452

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.506

Alfa AF: 0.523 Hom.: 4490

Bravo AF: 0.532

Asia WGS AF: 0.161 AC: 563 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.055
Dann	Benign	0.79

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: rs7541057; hg19: chr1-235860340;