rs1063128

Variant names:

• chr1-235809567-T-C
• rs1063128
• NM_000081.4:c.1251A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-235809567-T-C
• chr1-235809567-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000081.4(LYST):​c.1251A>G​(p.Gln417Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,380 control chromosomes in the GnomAD database, including 124,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13179 hom., cov: 31)
  • Exomes 𝑓: 0.38 (111264 hom.)
• Consequence: LYST NM_000081.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8 O:1
• Conservation: PhyloP100: -0.0510
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-235809567-T-C is Benign according to our data. Variant chr1-235809567-T-C is described in ClinVar as Benign. ClinVar VariationId is 254910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.051 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 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.1251A>G	p.Gln417Gln	synonymous	Exon 5 of 53	NP_000072.2	Q99698-1
	LYST	NM_001301365.1		c.1251A>G	p.Gln417Gln	synonymous	Exon 5 of 53	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.1251A>G	p.Gln417Gln	synonymous	Exon 5 of 53	ENSP00000374443.2	Q99698-1
	LYST	ENST00000465349.5	TSL:1	n.1802A>G		non_coding_transcript_exon	Exon 5 of 12
	LYST	ENST00000489585.5	TSL:1	n.1251A>G		non_coding_transcript_exon	Exon 5 of 23	ENSP00000513166.1	Q99698-2

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61533 AN: 151790 Hom.: 13165 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.394

GnomAD2 exomes AF: 0.345 AC: 86432 AN: 250608 AF XY: 0.339

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.0588

Gnomad FIN exome AF: 0.435

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.382 AC: 558950 AN: 1461472 Hom.: 111264 Cov.: 42 AF XY: 0.377 AC XY: 274165 AN XY: 727034

African (AFR) AF: 0.500 AC: 16738 AN: 33458

American (AMR) AF: 0.285 AC: 12733 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 9553 AN: 26130

East Asian (EAS) AF: 0.0857 AC: 3403 AN: 39686

South Asian (SAS) AF: 0.210 AC: 18128 AN: 86252

European-Finnish (FIN) AF: 0.435 AC: 23204 AN: 53388

Middle Eastern (MID) AF: 0.326 AC: 1879 AN: 5768

European-Non Finnish (NFE) AF: 0.406 AC: 451169 AN: 1111686

Other (OTH) AF: 0.367 AC: 22143 AN: 60390

GnomAD4 genome AF: 0.405 AC: 61595 AN: 151908 Hom.: 13179 Cov.: 31 AF XY: 0.398 AC XY: 29561 AN XY: 74216

African (AFR) AF: 0.495 AC: 20485 AN: 41396

American (AMR) AF: 0.327 AC: 5004 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1247 AN: 3466

East Asian (EAS) AF: 0.0625 AC: 323 AN: 5172

South Asian (SAS) AF: 0.195 AC: 940 AN: 4816

European-Finnish (FIN) AF: 0.434 AC: 4565 AN: 10518

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27738 AN: 67944

Other (OTH) AF: 0.391 AC: 825 AN: 2108

Alfa AF: 0.404 Hom.: 19985

Bravo AF: 0.402

Asia WGS AF: 0.156 AC: 546 AN: 3478

EpiCase AF: 0.392

EpiControl AF: 0.400

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Chédiak-Higashi syndrome (2)
-	-	2	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.9
DANN	Benign	0.28
PhyloP100		-0.051
Mutation Taster		=96/4	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: rs1063128; hg19: chr1-235972867; COSMIC: COSV67705101;