10-89222130-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000235.4(LIPA):c.894+381A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,134 control chromosomes in the GnomAD database, including 4,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.20 (4782 hom., cov: 32)
• Consequence: LIPA NM_000235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-89222130-T-G is Benign according to our data. Variant chr10-89222130-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPA	NM_000235.4	c.894+381A>C		intron_variant		ENST00000336233.10
LIPA	NM_001127605.3	c.894+381A>C		intron_variant
LIPA	NM_001288979.2	c.546+381A>C		intron_variant
LIPA	XM_024448023.2	c.894+381A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPA	ENST00000336233.10	c.894+381A>C		intron_variant		1	NM_000235.4	P1
LIPA	ENST00000371837.5	c.726+381A>C		intron_variant		2
LIPA	ENST00000456827.5	c.546+381A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29926 AN: 151018 Hom.: 4770 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.198 AC: 29959 AN: 151134 Hom.: 4782 Cov.: 32 AF XY: 0.213 AC XY: 15726 AN XY: 73862

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.208

Alfa AF: 0.191 Hom.: 4413

Bravo AF: 0.196

Asia WGS AF: 0.543 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.8
Dann	Benign	0.64

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: rs7922269; hg19: chr10-90981887; COSMIC: COSV51078377; COSMIC: COSV51078377;