dbSNP rs3738519: LYST:c.6881+44A>G (chr1-235758928-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.83

Variant links:

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]

LYST links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
LYST	NM_000081.4 link	c.6881+44A>G		intron_variant	Intron 23 of 52	ENST00000389793.7	NP_000072.2	Q99698-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7 link	c.6881+44A>G		intron_variant	Intron 23 of 52	5	NM_000081.4	ENSP00000374443.2		Q99698-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45117

AN:

151964

Hom.:

7328

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.251

AC XY:

179980

AN XY:

716610

show subpopulations

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.:

AF XY:

0.294

AC XY:

21876

AN XY:

74330

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:2

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 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

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

- -

Jul 15, 2018

GeneDx

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

-0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over