rs1131706

Variant names:

• chr10-89213919-A-T
• rs1131706
• NM_000235.4:c.*909T>A

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.*909T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,178 control chromosomes in the GnomAD database, including 4,601 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4601 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: LIPA NM_000235.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.515
• Publications: 8 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: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Genomics England PanelApp, Ambry Genetics
• 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=-0.78).
• BP6: Variant 10-89213919-A-T is Benign according to our data. Variant chr10-89213919-A-T is described in ClinVar as Benign. ClinVar VariationId is 301555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 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.*909T>A		3_prime_UTR	Exon 10 of 10	NP_000226.2	P38571-1
	LIPA	NM_001440836.1		c.*909T>A		3_prime_UTR	Exon 11 of 11	NP_001427765.1
	LIPA	NM_001440837.1		c.*909T>A		3_prime_UTR	Exon 10 of 10	NP_001427766.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPA	ENST00000336233.10	TSL:1 MANE Select	c.*909T>A		3_prime_UTR	Exon 10 of 10	ENSP00000337354.5	P38571-1
	LIPA	ENST00000868683.1		c.*909T>A		3_prime_UTR	Exon 10 of 10	ENSP00000538742.1
	LIPA	ENST00000938134.1		c.*909T>A		3_prime_UTR	Exon 10 of 10	ENSP00000608193.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31823 AN: 152058 Hom.: 4579 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.209 AC: 31879 AN: 152176 Hom.: 4601 Cov.: 32 AF XY: 0.204 AC XY: 15185 AN XY: 74396

African (AFR) AF: 0.409 AC: 16977 AN: 41468

American (AMR) AF: 0.121 AC: 1852 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3468

East Asian (EAS) AF: 0.0407 AC: 211 AN: 5190

South Asian (SAS) AF: 0.0975 AC: 471 AN: 4830

European-Finnish (FIN) AF: 0.134 AC: 1423 AN: 10594

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10192 AN: 68010

Other (OTH) AF: 0.177 AC: 373 AN: 2110

Alfa AF: 0.181 Hom.: 418

Bravo AF: 0.217

Asia WGS AF: 0.118 AC: 415 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Lysosomal acid lipase deficiency (1)
-	-	1	Wolman disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.5
DANN	Benign	0.89
PhyloP100		-0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1131706; hg19: chr10-90973676;