rs7541057

Variant names:

• chr1-235697040-C-T
• rs7541057
• NM_000081.4:c.10564+43G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-235697040-C-T
• chr1-235697040-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000081.4(LYST):​c.10564+43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,571,076 control chromosomes in the GnomAD database, including 195,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (23488 hom., cov: 32)
  • Exomes 𝑓: 0.48 (172068 hom.)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.88
• Publications: 7 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

ENSG00000296841 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-235697040-C-T is Benign according to our data. Variant chr1-235697040-C-T is described in ClinVar as Benign. ClinVar VariationId is 254908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 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.10564+43G>A		intron	N/A	NP_000072.2	Q99698-1
	LYST	NM_001301365.1		c.10564+43G>A		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.10564+43G>A		intron	N/A	ENSP00000374443.2	Q99698-1
	LYST	ENST00000697235.1		c.1114+43G>A		intron	N/A	ENSP00000513202.1	A0A8V8TL78
	LYST	ENST00000697179.1		n.3316G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80881 AN: 152004 Hom.: 23439 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.509

GnomAD2 exomes AF: 0.420 AC: 103367 AN: 245900 AF XY: 0.412

Gnomad AFR exome AF: 0.731

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.0498

Gnomad FIN exome AF: 0.535

Gnomad NFE exome AF: 0.515

Gnomad OTH exome AF: 0.459

GnomAD4 exome AF: 0.477 AC: 676800 AN: 1418954 Hom.: 172068 Cov.: 23 AF XY: 0.468 AC XY: 331761 AN XY: 708282

African (AFR) AF: 0.726 AC: 23728 AN: 32692

American (AMR) AF: 0.286 AC: 12676 AN: 44272

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12778 AN: 25826

East Asian (EAS) AF: 0.0509 AC: 2006 AN: 39422

South Asian (SAS) AF: 0.189 AC: 16037 AN: 84886

European-Finnish (FIN) AF: 0.540 AC: 28758 AN: 53240

Middle Eastern (MID) AF: 0.456 AC: 2574 AN: 5646

European-Non Finnish (NFE) AF: 0.513 AC: 550912 AN: 1074010

Other (OTH) AF: 0.464 AC: 27331 AN: 58960

GnomAD4 genome AF: 0.532 AC: 80978 AN: 152122 Hom.: 23488 Cov.: 32 AF XY: 0.519 AC XY: 38594 AN XY: 74356

African (AFR) AF: 0.722 AC: 29967 AN: 41498

American (AMR) AF: 0.381 AC: 5814 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1696 AN: 3470

East Asian (EAS) AF: 0.0452 AC: 234 AN: 5180

South Asian (SAS) AF: 0.171 AC: 823 AN: 4822

European-Finnish (FIN) AF: 0.534 AC: 5655 AN: 10580

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35139 AN: 67976

Other (OTH) AF: 0.506 AC: 1068 AN: 2112

Alfa AF: 0.523 Hom.: 4490

Bravo AF: 0.532

Asia WGS AF: 0.161 AC: 563 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.055
DANN	Benign	0.79
PhyloP100		-1.9
Mutation Taster		=24/76	disease causing

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: rs7541057; hg19: chr1-235860340;