rs2071509

Variant names:

• chr10-89228493-C-G
• rs2071509
• NM_000235.4:c.230-95G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-89228493-C-G
• chr10-89228493-C-A
• chr10-89228493-C-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.230-95G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 994,336 control chromosomes in the GnomAD database, including 127,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16889 hom., cov: 32)
  • Exomes 𝑓: 0.51 (110722 hom.)
• Consequence: LIPA NM_000235.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.662
• Publications: 10 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 Submitted by: ClinGen
• lysosomal acid lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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=-0.82).
• BP6: Variant 10-89228493-C-G is Benign according to our data. Variant chr10-89228493-C-G is described in ClinVar as Benign. ClinVar VariationId is 684271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000235.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPA	NM_000235.4	MANE Select	c.230-95G>C		intron	N/A	NP_000226.2	P38571-1
	LIPA	NM_001440836.1		c.362-95G>C		intron	N/A	NP_001427765.1
	LIPA	NM_001440837.1		c.230-95G>C		intron	N/A	NP_001427766.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPA	ENST00000336233.10	TSL:1 MANE Select	c.230-95G>C		intron	N/A	ENSP00000337354.5	P38571-1
	LIPA	ENST00000428800.5	TSL:1	c.230-95G>C		intron	N/A	ENSP00000388415.1	Q5T073
	LIPA	ENST00000868683.1		c.230-95G>C		intron	N/A	ENSP00000538742.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70275 AN: 151810 Hom.: 16871 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.468

GnomAD4 exome AF: 0.509 AC: 428726 AN: 842406 Hom.: 110722 AF XY: 0.510 AC XY: 224771 AN XY: 440510

African (AFR) AF: 0.333 AC: 7265 AN: 21812

American (AMR) AF: 0.415 AC: 16854 AN: 40634

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 12580 AN: 21980

East Asian (EAS) AF: 0.477 AC: 17420 AN: 36516

South Asian (SAS) AF: 0.486 AC: 34844 AN: 71734

European-Finnish (FIN) AF: 0.529 AC: 27053 AN: 51128

Middle Eastern (MID) AF: 0.526 AC: 1806 AN: 3436

European-Non Finnish (NFE) AF: 0.524 AC: 291184 AN: 555274

Other (OTH) AF: 0.494 AC: 19720 AN: 39892

GnomAD4 genome AF: 0.463 AC: 70335 AN: 151930 Hom.: 16889 Cov.: 32 AF XY: 0.466 AC XY: 34621 AN XY: 74254

African (AFR) AF: 0.336 AC: 13907 AN: 41424

American (AMR) AF: 0.449 AC: 6859 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1969 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2191 AN: 5166

South Asian (SAS) AF: 0.474 AC: 2284 AN: 4820

European-Finnish (FIN) AF: 0.546 AC: 5753 AN: 10534

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35840 AN: 67926

Other (OTH) AF: 0.470 AC: 991 AN: 2108

Alfa AF: 0.505 Hom.: 2480

Bravo AF: 0.445

Asia WGS AF: 0.444 AC: 1540 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.8
DANN	Benign	0.58
PhyloP100		0.66
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: rs2071509; hg19: chr10-90988250;