chr1-235758928-T-C

Position:

• chr1-235758928-T-C

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.6881+44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,590,076 control chromosomes in the GnomAD database, including 56,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7337 hom., cov: 32)
  • Exomes 𝑓: 0.25 (49419 hom.)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.83

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=-0.85).
• BP6: Variant 1-235758928-T-C is Benign according to our data. Variant chr1-235758928-T-C is described in ClinVar as [Benign]. Clinvar id is 254935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYST	NM_000081.4	c.6881+44A>G		intron_variant		ENST00000389793.7	NP_000072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7	c.6881+44A>G		intron_variant		5	NM_000081.4	ENSP00000374443.2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45117 AN: 151964 Hom.: 7328 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.270

GnomAD3 exomes AF: 0.241 AC: 59938 AN: 248736 Hom.: 8350 AF XY: 0.236 AC XY: 31812 AN XY: 134742

Gnomad AFR exome AF: 0.426

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.00940

Gnomad SAS exome AF: 0.168

Gnomad FIN exome AF: 0.339

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.255 AC: 366148 AN: 1437994 Hom.: 49419 Cov.: 28 AF XY: 0.251 AC XY: 179980 AN XY: 716610

Gnomad4 AFR exome AF: 0.421

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.0364

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.334

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.297 AC: 45177 AN: 152082 Hom.: 7337 Cov.: 32 AF XY: 0.294 AC XY: 21876 AN XY: 74330

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.269

Alfa AF: 0.268 Hom.: 1618

Bravo AF: 0.292

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.024
DANN	Benign	0.47

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: rs3738519; hg19: chr1-235922228;