rs17615059

chr1-235702714-T-Cchr1-235702714-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000081.4(LYST):c.10374+33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,562,692 control chromosomes in the GnomAD database, including 808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (46 hom., cov: 32)
  • Exomes 𝑓: 0.030 (762 hom.)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.462

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=-0.66).
• BP6: Variant 1-235702714-T-C is Benign according to our data. Variant chr1-235702714-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 254907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-235702714-T-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0217 (3305/152270) while in subpopulation NFE AF= 0.0339 (2303/68014). AF 95% confidence interval is 0.0327. There are 46 homozygotes in gnomad4. There are 1511 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYST	NM_000081.4	c.10374+33A>G		intron_variant		ENST00000389793.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYST	ENST00000389793.7	c.10374+33A>G		intron_variant		5	NM_000081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3310 AN: 152152 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.00615

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00809

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0227 AC: 5684 AN: 250188 Hom.: 93 AF XY: 0.0237 AC XY: 3213 AN XY: 135398

Gnomad AFR exome AF: 0.00492

Gnomad AMR exome AF: 0.0116

Gnomad ASJ exome AF: 0.0444

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0111

Gnomad FIN exome AF: 0.0185

Gnomad NFE exome AF: 0.0341

Gnomad OTH exome AF: 0.0296

GnomAD4 exome AF: 0.0305 AC: 42962 AN: 1410422 Hom.: 762 Cov.: 25 AF XY: 0.0297 AC XY: 20951 AN XY: 704894

Gnomad4 AFR exome AF: 0.00514

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.0448

Gnomad4 EAS exome AF: 0.0000761

Gnomad4 SAS exome AF: 0.0110

Gnomad4 FIN exome AF: 0.0212

Gnomad4 NFE exome AF: 0.0349

Gnomad4 OTH exome AF: 0.0290

GnomAD4 genome AF: 0.0217 AC: 3305 AN: 152270 Hom.: 46 Cov.: 32 AF XY: 0.0203 AC XY: 1511 AN XY: 74454

Gnomad4 AFR AF: 0.00614

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00789

Gnomad4 FIN AF: 0.0162

Gnomad4 NFE AF: 0.0339

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0201 Hom.: 11

Bravo AF: 0.0210

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	7.9
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs17615059; hg19: chr1-235866014;