Variant chr10-89215892-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000235.4(LIPA):c.966+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,248,724 control chromosomes in the GnomAD database, including 39,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7240 hom., cov: 32)

Exomes 𝑓: 0.23 ( 32211 hom. )

Consequence

LIPA
NM_000235.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.270

Variant links:

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]

LIPA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-89215892-G-A is Benign according to our data. Variant chr10-89215892-G-A is described in ClinVar as [Benign]. Clinvar id is 255613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-89215892-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
LIPA	NM_000235.4 linkuse as main transcript	c.966+46C>T	intron_variant	ENST00000336233.10
LIPA	NM_001127605.3 linkuse as main transcript	c.966+46C>T	intron_variant
LIPA	NM_001288979.2 linkuse as main transcript	c.618+46C>T	intron_variant
LIPA	XM_024448023.2 linkuse as main transcript	c.966+46C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
LIPA	ENST00000336233.10 linkuse as main transcript	c.966+46C>T	intron_variant	1	NM_000235.4	P1	P38571-1
LIPA	ENST00000371837.5 linkuse as main transcript	c.798+46C>T	intron_variant	2			P38571-2
LIPA	ENST00000456827.5 linkuse as main transcript	c.618+46C>T	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43069

AN:

151992

Hom.:

7217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.0331

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.328

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.262

GnomAD3 exomes

AF:

0.211

AC:

52798

AN:

250550

Hom.:

6541

AF XY:

0.211

AC XY:

28602

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.459

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.0290

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.219

GnomAD4 exome

AF:

0.233

AC:

255184

AN:

1096612

Hom.:

32211

Cov.:

AF XY:

0.231

AC XY:

129985

AN XY:

562368

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.0255

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.237

GnomAD4 genome

AF:

0.284

AC:

43139

AN:

152112

Hom.:

7240

Cov.:

AF XY:

0.276

AC XY:

20509

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.462

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.0332

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.256

Hom.:

1315

Bravo

AF:

0.292

Asia WGS

AF:

0.158

AC:

552

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Lysosomal acid lipase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over