rs6494005

Variant names:

• chr15-58432325-A-G
• rs6494005
• NM_000236.3:c.88+205A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-58432325-A-G
• chr15-58432325-A-T

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+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 607,666 control chromosomes in the GnomAD database, including 67,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (13731 hom., cov: 33)
  • Exomes 𝑓: 0.47 (54121 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0810
• Publications: 20 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: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-58432325-A-G is Benign according to our data. Variant chr15-58432325-A-G is described in ClinVar as Benign. ClinVar VariationId is 1264908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.88+205A>G		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.88+205A>G		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57570 AN: 152018 Hom.: 13731 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.474 AC: 216035 AN: 455530 Hom.: 54121 Cov.: 3 AF XY: 0.475 AC XY: 115248 AN XY: 242456

African (AFR) AF: 0.106 AC: 1332 AN: 12614

American (AMR) AF: 0.327 AC: 6983 AN: 21344

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 7459 AN: 14320

East Asian (EAS) AF: 0.253 AC: 7664 AN: 30348

South Asian (SAS) AF: 0.436 AC: 20353 AN: 46648

European-Finnish (FIN) AF: 0.486 AC: 13804 AN: 28422

Middle Eastern (MID) AF: 0.550 AC: 1247 AN: 2268

European-Non Finnish (NFE) AF: 0.531 AC: 145115 AN: 273458

Other (OTH) AF: 0.463 AC: 12078 AN: 26108

GnomAD4 genome AF: 0.378 AC: 57555 AN: 152136 Hom.: 13731 Cov.: 33 AF XY: 0.375 AC XY: 27879 AN XY: 74366

African (AFR) AF: 0.101 AC: 4214 AN: 41536

American (AMR) AF: 0.375 AC: 5730 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1750 AN: 3466

East Asian (EAS) AF: 0.240 AC: 1245 AN: 5180

South Asian (SAS) AF: 0.410 AC: 1975 AN: 4820

European-Finnish (FIN) AF: 0.473 AC: 5006 AN: 10580

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36023 AN: 67962

Other (OTH) AF: 0.409 AC: 863 AN: 2112

Alfa AF: 0.473 Hom.: 57512

Bravo AF: 0.357

Asia WGS AF: 0.289 AC: 1009 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

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	-0.80
CADD	Benign	4.9
DANN	Benign	0.64
PhyloP100		0.081
PromoterAI		0.0088	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: rs6494005; hg19: chr15-58724524;