rs11631342

Variant names:

• chr15-58432184-A-G
• rs11631342
• NM_000236.3:c.88+64A>G

Variant summary

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

The NM_000236.3(LIPC):​c.88+64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 1,220,094 control chromosomes in the GnomAD database, including 1,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (453 hom., cov: 32)
  • Exomes 𝑓: 0.021 (610 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.183
• Publications: 10 publications found

Genes affected

LIPC (HGNC:6619): (lipase C, hepatic type) Enables phospholipase A1 activity and triglyceride lipase activity. Involved in several processes, including lipid homeostasis; plasma lipoprotein particle remodeling; and triglyceride catabolic process. Located in extracellular space. Implicated in several diseases, including Alzheimer's disease; coronary artery disease; familial combined hyperlipidemia; peripheral vascular disease; and type 2 diabetes mellitus. Biomarker of hyperinsulinism; obesity; and type 1 diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

ALDH1A2 Gene-Disease associations (from GenCC):

• diaphragmatic hernia 4, with cardiovascular defects

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 15-58432184-A-G is Benign according to our data. Variant chr15-58432184-A-G is described in ClinVar as Benign. ClinVar VariationId is 1243737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000236.3. 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
	LIPC	NM_000236.3	MANE Select	c.88+64A>G		intron	N/A	NP_000227.2	P11150

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.88+64A>G		intron	N/A	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.88+64A>G		intron	N/A	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.130+64A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 8312 AN: 152178 Hom.: 450 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.0553

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0501

GnomAD4 exome AF: 0.0207 AC: 22078 AN: 1067798 Hom.: 610 Cov.: 14 AF XY: 0.0211 AC XY: 11620 AN XY: 549612

African (AFR) AF: 0.142 AC: 3691 AN: 25980

American (AMR) AF: 0.0408 AC: 1797 AN: 44016

Ashkenazi Jewish (ASJ) AF: 0.0301 AC: 710 AN: 23584

East Asian (EAS) AF: 0.0591 AC: 2243 AN: 37936

South Asian (SAS) AF: 0.0438 AC: 3430 AN: 78310

European-Finnish (FIN) AF: 0.0248 AC: 1315 AN: 53072

Middle Eastern (MID) AF: 0.0426 AC: 214 AN: 5022

European-Non Finnish (NFE) AF: 0.00964 AC: 7252 AN: 752490

Other (OTH) AF: 0.0301 AC: 1426 AN: 47388

GnomAD4 genome AF: 0.0547 AC: 8324 AN: 152296 Hom.: 453 Cov.: 32 AF XY: 0.0556 AC XY: 4143 AN XY: 74482

African (AFR) AF: 0.137 AC: 5709 AN: 41540

American (AMR) AF: 0.0472 AC: 722 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3470

East Asian (EAS) AF: 0.0638 AC: 331 AN: 5190

South Asian (SAS) AF: 0.0551 AC: 266 AN: 4826

European-Finnish (FIN) AF: 0.0298 AC: 316 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 761 AN: 68038

Other (OTH) AF: 0.0496 AC: 105 AN: 2116

Alfa AF: 0.0238 Hom.: 239

Bravo AF: 0.0591

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.64
CADD	Benign	5.9
DANN	Benign	0.77
PhyloP100		0.18
PromoterAI		0.051	Neutral
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: rs11631342; hg19: chr15-58724383; COSMIC: COSV54427924; COSMIC: COSV54427924;