rs1063128

Variant names:

• chr1-235809567-T-C
• rs1063128
• NM_000081.4:c.1251A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-235809567-T-C
• chr1-235809567-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000081.4(LYST):​c.1251A>G​(p.Gln417Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,380 control chromosomes in the GnomAD database, including 124,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13179 hom., cov: 31)
  • Exomes 𝑓: 0.38 (111264 hom.)
• Consequence: LYST NM_000081.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -0.0510

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-235809567-T-C is Benign according to our data. Variant chr1-235809567-T-C is described in ClinVar as [Benign]. Clinvar id is 254910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.051 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4	c.1251A>G	p.Gln417Gln	synonymous_variant	Exon 5 of 53	ENST00000389793.7	NP_000072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7	c.1251A>G	p.Gln417Gln	synonymous_variant	Exon 5 of 53	5	NM_000081.4	ENSP00000374443.2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61533 AN: 151790 Hom.: 13165 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.394

GnomAD2 exomes AF: 0.345 AC: 86432 AN: 250608 AF XY: 0.339

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.0588

Gnomad FIN exome AF: 0.435

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.382 AC: 558950 AN: 1461472 Hom.: 111264 Cov.: 42 AF XY: 0.377 AC XY: 274165 AN XY: 727034

Gnomad4 AFR exome AF: 0.500 AC: 16738 AN: 33458

Gnomad4 AMR exome AF: 0.285 AC: 12733 AN: 44714

Gnomad4 ASJ exome AF: 0.366 AC: 9553 AN: 26130

Gnomad4 EAS exome AF: 0.0857 AC: 3403 AN: 39686

Gnomad4 SAS exome AF: 0.210 AC: 18128 AN: 86252

Gnomad4 FIN exome AF: 0.435 AC: 23204 AN: 53388

Gnomad4 NFE exome AF: 0.406 AC: 451169 AN: 1111686

Gnomad4 Remaining exome AF: 0.367 AC: 22143 AN: 60390

GnomAD4 genome AF: 0.405 AC: 61595 AN: 151908 Hom.: 13179 Cov.: 31 AF XY: 0.398 AC XY: 29561 AN XY: 74216

Gnomad4 AFR AF: 0.495 AC: 0.494855 AN: 0.494855

Gnomad4 AMR AF: 0.327 AC: 0.327444 AN: 0.327444

Gnomad4 ASJ AF: 0.360 AC: 0.359781 AN: 0.359781

Gnomad4 EAS AF: 0.0625 AC: 0.0624517 AN: 0.0624517

Gnomad4 SAS AF: 0.195 AC: 0.195183 AN: 0.195183

Gnomad4 FIN AF: 0.434 AC: 0.434018 AN: 0.434018

Gnomad4 NFE AF: 0.408 AC: 0.408248 AN: 0.408248

Gnomad4 OTH AF: 0.391 AC: 0.391366 AN: 0.391366

Alfa AF: 0.404 Hom.: 19985

Bravo AF: 0.402

Asia WGS AF: 0.156 AC: 546 AN: 3478

EpiCase AF: 0.392

EpiControl AF: 0.400

ClinVar

Significance: Benign

Submissions summary: Benign:7 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 50% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided Benign:2 Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Jun 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Chédiak-Higashi syndrome Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.9
DANN	Benign	0.28
Mutation Taster		=96/4	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

Publications

LitVar

Other links and lift over

dbSNP: rs1063128; hg19: chr1-235972867; COSMIC: COSV67705101;