rs11594137

Positions:

• chr10-89215450-A-C
• chr10-89215450-A-T

Variant summary

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

The NM_000235.4(LIPA):​c.967-389T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,250 control chromosomes in the GnomAD database, including 1,038 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 0.11 (1038 hom., cov: 32)
• Consequence: LIPA NM_000235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

Genes affected

LIPA (HGNC:6617): (lipase A, lysosomal acid type) This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase). This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides. Mutations in this gene can result in Wolman disease and cholesteryl ester storage disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPA	NM_000235.4	c.967-389T>G		intron_variant		ENST00000336233.10	NP_000226.2
LIPA	NM_001127605.3	c.967-389T>G		intron_variant			NP_001121077.1
LIPA	NM_001288979.2	c.619-389T>G		intron_variant			NP_001275908.1
LIPA	XM_024448023.2	c.967-389T>G		intron_variant			XP_024303791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPA	ENST00000336233.10	c.967-389T>G		intron_variant		1	NM_000235.4	ENSP00000337354	P1
LIPA	ENST00000371837.5	c.799-389T>G		intron_variant		2		ENSP00000360903
LIPA	ENST00000456827.5	c.619-389T>G		intron_variant		3		ENSP00000413019

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16547 AN: 152132 Hom.: 1038 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0544

Gnomad EAS AF: 0.0267

Gnomad SAS AF: 0.0912

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.0988

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

GnomAD4 genome AF: 0.109 AC: 16552 AN: 152250 Hom.: 1038 Cov.: 32 AF XY: 0.107 AC XY: 7947 AN XY: 74428

Gnomad4 AFR AF: 0.0811

Gnomad4 AMR AF: 0.0750

Gnomad4 ASJ AF: 0.0544

Gnomad4 EAS AF: 0.0268

Gnomad4 SAS AF: 0.0902

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.0991

Alfa AF: 0.123 Hom.: 1841

Bravo AF: 0.104

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.67

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: rs11594137; hg19: chr10-90975207;