rs3802656

Variant names:

• chr10-89215892-G-A
• rs3802656
• NM_000235.4:c.966+46C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-89215892-G-A
• chr10-89215892-G-C
• chr10-89215892-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.270
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• lysosomal acid lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
• cholesteryl ester storage disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Wolman disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPA	NM_000235.4	c.966+46C>T		intron_variant	Intron 9 of 9	ENST00000336233.10	NP_000226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPA	ENST00000336233.10	c.966+46C>T		intron_variant	Intron 9 of 9	1	NM_000235.4	ENSP00000337354.5
LIPA	ENST00000371837.5	c.798+46C>T		intron_variant	Intron 8 of 8	2		ENSP00000360903.1
LIPA	ENST00000456827.5	c.618+46C>T		intron_variant	Intron 7 of 7	3		ENSP00000413019.2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43069 AN: 151992 Hom.: 7217 Cov.: 32

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

GnomAD2 exomes AF: 0.211 AC: 52798 AN: 250550 AF XY: 0.211

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 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.: 15 AF XY: 0.231 AC XY: 129985 AN XY: 562368

African (AFR) AF: 0.464 AC: 12199 AN: 26302

American (AMR) AF: 0.147 AC: 6502 AN: 44286

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 4835 AN: 23892

East Asian (EAS) AF: 0.0255 AC: 971 AN: 38098

South Asian (SAS) AF: 0.182 AC: 14390 AN: 78922

European-Finnish (FIN) AF: 0.180 AC: 9585 AN: 53258

Middle Eastern (MID) AF: 0.241 AC: 1212 AN: 5026

European-Non Finnish (NFE) AF: 0.249 AC: 194029 AN: 778508

Other (OTH) AF: 0.237 AC: 11461 AN: 48320

GnomAD4 genome AF: 0.284 AC: 43139 AN: 152112 Hom.: 7240 Cov.: 32 AF XY: 0.276 AC XY: 20509 AN XY: 74358

African (AFR) AF: 0.462 AC: 19161 AN: 41456

American (AMR) AF: 0.181 AC: 2761 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3472

East Asian (EAS) AF: 0.0332 AC: 172 AN: 5180

South Asian (SAS) AF: 0.172 AC: 827 AN: 4822

European-Finnish (FIN) AF: 0.172 AC: 1824 AN: 10586

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16818 AN: 67990

Other (OTH) AF: 0.260 AC: 550 AN: 2116

Alfa AF: 0.295 Hom.: 4640

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

Submissions by phenotype

not provided Benign:2

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lysosomal acid lipase deficiency Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3802656; hg19: chr10-90975649;