rs3768051

Positions:

• chr1-235696414-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000081.4(LYST):​c.10564+669C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0771 in 152,274 control chromosomes in the GnomAD database, including 509 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.077 (509 hom., cov: 32)
• Consequence: LYST NM_000081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYST	NM_000081.4	c.10564+669C>A		intron_variant		ENST00000389793.7	NP_000072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7	c.10564+669C>A		intron_variant		5	NM_000081.4	ENSP00000374443	P1

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11748 AN: 152156 Hom.: 510 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0902

Gnomad OTH AF: 0.0910

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0771 AC: 11745 AN: 152274 Hom.: 509 Cov.: 32 AF XY: 0.0748 AC XY: 5569 AN XY: 74444

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.0861

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0432

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.0611

Gnomad4 NFE AF: 0.0902

Gnomad4 OTH AF: 0.0896

Alfa AF: 0.0847 Hom.: 295

Bravo AF: 0.0807

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0020
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs3768051; hg19: chr1-235859714; COSMIC: COSV67704846;