rs9803890

Positions:

• chr1-235801123-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.3713-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00803 in 1,325,518 control chromosomes in the GnomAD database, including 614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (342 hom., cov: 31)
  • Exomes 𝑓: 0.0043 (272 hom.)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.966

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=-0.7).
• BP6: Variant 1-235801123-C-T is Benign according to our data. Variant chr1-235801123-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 254919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYST	NM_000081.4	c.3713-26G>A		intron_variant		ENST00000389793.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYST	ENST00000389793.7	c.3713-26G>A		intron_variant		5	NM_000081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5611 AN: 152100 Hom.: 341 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00987 AC: 2433 AN: 246442 Hom.: 143 AF XY: 0.00761 AC XY: 1019 AN XY: 133940

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.00646

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.0000518

Gnomad NFE exome AF: 0.000552

Gnomad OTH exome AF: 0.00564

GnomAD4 exome AF: 0.00428 AC: 5018 AN: 1173300 Hom.: 272 Cov.: 17 AF XY: 0.00364 AC XY: 2173 AN XY: 597752

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.00746

Gnomad4 ASJ exome AF: 0.0000409

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.000311

Gnomad4 FIN exome AF: 0.0000796

Gnomad4 NFE exome AF: 0.000337

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0370 AC: 5631 AN: 152218 Hom.: 342 Cov.: 31 AF XY: 0.0350 AC XY: 2608 AN XY: 74426

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0233 Hom.: 29

Bravo AF: 0.0431

Asia WGS AF: 0.0130 AC: 44 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.8
DANN	Benign	0.68

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: rs9803890; hg19: chr1-235964423;