rs16832868

Variant names:

• chr1-235808502-G-A
• rs16832868
• NM_000081.4:c.2316C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-235808502-G-A
• chr1-235808502-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000081.4(LYST):​c.2316C>T​(p.Asp772Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,613,264 control chromosomes in the GnomAD database, including 1,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (767 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (624 hom.)
• Consequence: LYST NM_000081.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.03
• Publications: 3 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: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• attenuated Chédiak-Higashi syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 1-235808502-G-A is Benign according to our data. Variant chr1-235808502-G-A is described in ClinVar as Benign. ClinVar VariationId is 254914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	NM_000081.4	MANE Select	c.2316C>T	p.Asp772Asp	synonymous	Exon 5 of 53	NP_000072.2
	LYST	NM_001301365.1		c.2316C>T	p.Asp772Asp	synonymous	Exon 5 of 53	NP_001288294.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	ENST00000389793.7	TSL:5 MANE Select	c.2316C>T	p.Asp772Asp	synonymous	Exon 5 of 53	ENSP00000374443.2
	LYST	ENST00000465349.5	TSL:1	n.2867C>T		non_coding_transcript_exon	Exon 5 of 12
	LYST	ENST00000489585.5	TSL:1	n.2316C>T		non_coding_transcript_exon	Exon 5 of 23	ENSP00000513166.1

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 8229 AN: 151512 Hom.: 764 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0375

GnomAD2 exomes AF: 0.0143 AC: 3582 AN: 251138 AF XY: 0.0106

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.00892

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000731

Gnomad OTH exome AF: 0.00883

GnomAD4 exome AF: 0.00570 AC: 8333 AN: 1461634 Hom.: 624 Cov.: 35 AF XY: 0.00503 AC XY: 3655 AN XY: 727110

African (AFR) AF: 0.191 AC: 6395 AN: 33462

American (AMR) AF: 0.0105 AC: 469 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000429 AC: 37 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.0106 AC: 61 AN: 5762

European-Non Finnish (NFE) AF: 0.000486 AC: 540 AN: 1111870

Other (OTH) AF: 0.0130 AC: 784 AN: 60382

GnomAD4 genome AF: 0.0544 AC: 8255 AN: 151630 Hom.: 767 Cov.: 32 AF XY: 0.0527 AC XY: 3900 AN XY: 74034

African (AFR) AF: 0.189 AC: 7799 AN: 41266

American (AMR) AF: 0.0205 AC: 312 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10450

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 67972

Other (OTH) AF: 0.0371 AC: 78 AN: 2102

Alfa AF: 0.0265 Hom.: 234

Bravo AF: 0.0619

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000889

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.56
PhyloP100		2.0
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs16832868; hg19: chr1-235971802; COSMIC: COSV67712307;