rs11464

Variant names:

• chr1-235830265-T-G
• rs11464
• NM_000081.4:c.153A>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.153A>C​(p.Gly51Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,613,704 control chromosomes in the GnomAD database, including 7,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (3818 hom., cov: 32)
  • Exomes 𝑓: 0.014 (3534 hom.)
• Consequence: LYST NM_000081.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.185
• Publications: 1 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 1-235830265-T-G is Benign according to our data. Variant chr1-235830265-T-G is described in ClinVar as Benign. ClinVar VariationId is 254911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.185 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 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.153A>C	p.Gly51Gly	synonymous	Exon 3 of 53	NP_000072.2	Q99698-1
	LYST	NM_001301365.1		c.153A>C	p.Gly51Gly	synonymous	Exon 3 of 53	NP_001288294.1	Q99698-1
	LYST	NR_102436.3		n.777A>C		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	ENST00000389793.7	TSL:5 MANE Select	c.153A>C	p.Gly51Gly	synonymous	Exon 3 of 53	ENSP00000374443.2	Q99698-1
	LYST	ENST00000468626.2	TSL:1	c.153A>C	p.Gly51Gly	synonymous	Exon 3 of 3	ENSP00000513173.1	A0A8V8TKS8
	LYST	ENST00000468107.5	TSL:1	c.153A>C	p.Gly51Gly	synonymous	Exon 3 of 4	ENSP00000513172.1	A0A8V8TMC0

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18496 AN: 151926 Hom.: 3805 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.0929

GnomAD2 exomes AF: 0.0330 AC: 8292 AN: 251276 AF XY: 0.0241

Gnomad AFR exome AF: 0.442

Gnomad AMR exome AF: 0.0209

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.0181

GnomAD4 exome AF: 0.0135 AC: 19763 AN: 1461662 Hom.: 3534 Cov.: 31 AF XY: 0.0118 AC XY: 8545 AN XY: 727146

African (AFR) AF: 0.444 AC: 14839 AN: 33422

American (AMR) AF: 0.0236 AC: 1054 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00505 AC: 132 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00101 AC: 87 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.0284 AC: 164 AN: 5766

European-Non Finnish (NFE) AF: 0.00146 AC: 1619 AN: 1111894

Other (OTH) AF: 0.0309 AC: 1868 AN: 60380

GnomAD4 genome AF: 0.122 AC: 18551 AN: 152042 Hom.: 3818 Cov.: 32 AF XY: 0.117 AC XY: 8698 AN XY: 74370

African (AFR) AF: 0.422 AC: 17475 AN: 41376

American (AMR) AF: 0.0453 AC: 692 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00221 AC: 150 AN: 67994

Other (OTH) AF: 0.0924 AC: 195 AN: 2110

Alfa AF: 0.0931 Hom.: 2377

Bravo AF: 0.141

Asia WGS AF: 0.0350 AC: 122 AN: 3478

EpiCase AF: 0.00213

EpiControl AF: 0.00249

ClinVar

ClinVar submissions

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	7.3
DANN	Benign	0.72
PhyloP100		0.18
Mutation Taster		=99/1	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: rs11464; hg19: chr1-235993565;