rs11464

Variant names:

• chr1-235830265-T-G
• rs11464
• NM_000081.4:c.153A>C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000081.4(LYST):​c.153A>C​(p.Gly51Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,613,704 control chromosomes in the GnomAD database, including 7,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (3818 hom., cov: 32)
  • Exomes 𝑓: 0.014 (3534 hom.)
• Consequence: LYST NM_000081.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.185

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 1-235830265-T-G is Benign according to our data. Variant chr1-235830265-T-G is described in ClinVar as [Benign]. Clinvar id is 254911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.185 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4	c.153A>C	p.Gly51Gly	synonymous_variant	Exon 3 of 53	ENST00000389793.7	NP_000072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7	c.153A>C	p.Gly51Gly	synonymous_variant	Exon 3 of 53	5	NM_000081.4	ENSP00000374443.2

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18496 AN: 151926 Hom.: 3805 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.0929

GnomAD3 exomes AF: 0.0330 AC: 8292 AN: 251276 Hom.: 1644 AF XY: 0.0241 AC XY: 3272 AN XY: 135796

Gnomad AFR exome AF: 0.442

Gnomad AMR exome AF: 0.0209

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.0181

GnomAD4 exome AF: 0.0135 AC: 19763 AN: 1461662 Hom.: 3534 Cov.: 31 AF XY: 0.0118 AC XY: 8545 AN XY: 727146

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.0236

Gnomad4 ASJ exome AF: 0.00505

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00146

Gnomad4 OTH exome AF: 0.0309

GnomAD4 genome AF: 0.122 AC: 18551 AN: 152042 Hom.: 3818 Cov.: 32 AF XY: 0.117 AC XY: 8698 AN XY: 74370

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.0453

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00221

Gnomad4 OTH AF: 0.0924

Alfa AF: 0.0613 Hom.: 820

Bravo AF: 0.141

Asia WGS AF: 0.0350 AC: 122 AN: 3478

EpiCase AF: 0.00213

EpiControl AF: 0.00249

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Chédiak-Higashi syndrome Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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	-0.45
CADD	Benign	7.3
DANN	Benign	0.72

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: rs11464; hg19: chr1-235993565;