rs141197189

Variant names:

• chr1-235766296-C-A
• rs141197189
• NM_000081.4:c.5923-19G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-235766296-C-A
• chr1-235766296-C-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000081.4(LYST):​c.5923-19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,561,406 control chromosomes in the GnomAD database, including 1,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (99 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1669 hom.)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0930
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Chediak-Higashi syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp
• attenuated Chédiak-Higashi syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 1-235766296-C-A is Benign according to our data. Variant chr1-235766296-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000081.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	NM_000081.4	MANE Select	c.5923-19G>T		intron	N/A	NP_000072.2	Q99698-1
	LYST	NM_001301365.1		c.5923-19G>T		intron	N/A	NP_001288294.1	Q99698-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	ENST00000389793.7	TSL:5 MANE Select	c.5923-19G>T		intron	N/A	ENSP00000374443.2	Q99698-1
	LYST	ENST00000489585.5	TSL:1	n.5923-19G>T		intron	N/A	ENSP00000513166.1	Q99698-2
	LYST	ENST00000697241.1		c.355-19G>T		intron	N/A	ENSP00000513206.1	A0A8V8TM69

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4639 AN: 152024 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.00978

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0302

GnomAD2 exomes AF: 0.0306 AC: 6986 AN: 228040 AF XY: 0.0313

Gnomad AFR exome AF: 0.00755

Gnomad AMR exome AF: 0.0344

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0148

Gnomad NFE exome AF: 0.0437

Gnomad OTH exome AF: 0.0283

GnomAD4 exome AF: 0.0442 AC: 62349 AN: 1409264 Hom.: 1669 Cov.: 26 AF XY: 0.0434 AC XY: 30477 AN XY: 702872

African (AFR) AF: 0.00819 AC: 257 AN: 31366

American (AMR) AF: 0.0343 AC: 1337 AN: 38980

Ashkenazi Jewish (ASJ) AF: 0.0181 AC: 453 AN: 24986

East Asian (EAS) AF: 0.000203 AC: 8 AN: 39454

South Asian (SAS) AF: 0.0266 AC: 2161 AN: 81350

European-Finnish (FIN) AF: 0.0172 AC: 904 AN: 52702

Middle Eastern (MID) AF: 0.0142 AC: 79 AN: 5570

European-Non Finnish (NFE) AF: 0.0510 AC: 54928 AN: 1076498

Other (OTH) AF: 0.0381 AC: 2222 AN: 58358

GnomAD4 genome AF: 0.0305 AC: 4640 AN: 152142 Hom.: 99 Cov.: 32 AF XY: 0.0290 AC XY: 2156 AN XY: 74378

African (AFR) AF: 0.00975 AC: 405 AN: 41520

American (AMR) AF: 0.0406 AC: 620 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4822

European-Finnish (FIN) AF: 0.0143 AC: 152 AN: 10596

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0474 AC: 3220 AN: 67960

Other (OTH) AF: 0.0299 AC: 63 AN: 2108

Alfa AF: 0.0192 Hom.: 9

Bravo AF: 0.0323

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Chédiak-Higashi syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		-0.093
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs141197189; hg19: chr1-235929596;