1-235876577-T-C

Variant names:

• chr1-235876577-T-C
• rs9782955
• ENST00000468107.5:c.-98+6610A>G

Variant summary

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

The NM_001301365.1(LYST):​c.-98+6610A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,260 control chromosomes in the GnomAD database, including 51,562 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 0.82 (51562 hom., cov: 33)
• Consequence: LYST NM_001301365.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950

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 (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_001301365.1	c.-98+6610A>G		intron_variant	Intron 1 of 52		NP_001288294.1
LYST	XM_011544032.2	c.-98+6610A>G		intron_variant	Intron 1 of 53		XP_011542334.1
LYST	NR_102436.3	n.527+6610A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000468107.5	c.-98+6610A>G		intron_variant	Intron 1 of 3	1		ENSP00000513172.1
LYST	ENST00000465349.5	n.454+6610A>G		intron_variant	Intron 1 of 11	1
LYST	ENST00000489585.5	n.-98+6610A>G		intron_variant	Intron 1 of 22	1		ENSP00000513166.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124587 AN: 152142 Hom.: 51506 Cov.: 33

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.819 AC: 124703 AN: 152260 Hom.: 51562 Cov.: 33 AF XY: 0.821 AC XY: 61093 AN XY: 74442

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.882

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.806

Alfa AF: 0.764 Hom.: 58513

Bravo AF: 0.822

Asia WGS AF: 0.817 AC: 2838 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	0.50
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9782955; hg19: chr1-236039877;