rs12088737

chr1-235664645-G-A

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.11039-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,613,624 control chromosomes in the GnomAD database, including 3,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (1539 hom., cov: 31)
  • Exomes 𝑓: 0.0091 (1479 hom.)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.236

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=-0.74).
• BP6: Variant 1-235664645-G-A is Benign according to our data. Variant chr1-235664645-G-A is described in ClinVar as [Benign]. Clinvar id is 254909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYST	NM_000081.4	c.11039-24C>T		intron_variant		ENST00000389793.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYST	ENST00000389793.7	c.11039-24C>T		intron_variant		5	NM_000081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11963 AN: 152014 Hom.: 1536 Cov.: 31

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0613

GnomAD3 exomes AF: 0.0227 AC: 5669 AN: 249812 Hom.: 673 AF XY: 0.0173 AC XY: 2342 AN XY: 135242

Gnomad AFR exome AF: 0.284

Gnomad AMR exome AF: 0.0131

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0152

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000933

Gnomad OTH exome AF: 0.0128

GnomAD4 exome AF: 0.00906 AC: 13247 AN: 1461492 Hom.: 1479 Cov.: 32 AF XY: 0.00831 AC XY: 6041 AN XY: 727066

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.0000750

Gnomad4 NFE exome AF: 0.000609

Gnomad4 OTH exome AF: 0.0198

GnomAD4 genome AF: 0.0789 AC: 12008 AN: 152132 Hom.: 1539 Cov.: 31 AF XY: 0.0761 AC XY: 5661 AN XY: 74382

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.0342

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0183

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.0640

Alfa AF: 0.0166 Hom.: 285

Bravo AF: 0.0916

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Significance: 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

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	-0.74
Cadd	Benign	5.3
Dann	Benign	0.89

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: rs12088737; hg19: chr1-235827945;