rs2070895

Variant names:

• chr15-58431740-G-A
• rs2070895
• ENST00000414170.7:c.-40-253G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-58431740-G-A
• chr15-58431740-G-T

Variant summary

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

The ENST00000414170.7(LIPC):​c.-40-253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 447,094 control chromosomes in the GnomAD database, including 21,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9796 hom., cov: 32)
  • Exomes 𝑓: 0.26 (11482 hom.)
• Consequence: LIPC ENST00000414170.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:2
• Conservation: PhyloP100: 0.453
• Publications: 161 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=-0.84).
• BP6: Variant 15-58431740-G-A is Benign according to our data. Variant chr15-58431740-G-A is described in ClinVar as Benign. ClinVar VariationId is 14454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000414170.7. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000414170.7	TSL:1	c.-40-253G>A		intron	N/A	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000901649.1		c.-77G>A		5_prime_UTR	Exon 1 of 10	ENSP00000571708.1
	LIPC	ENST00000901642.1		c.-40-253G>A		intron	N/A	ENSP00000571701.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50467 AN: 151884 Hom.: 9765 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.260 AC: 76715 AN: 295092 Hom.: 11482 AF XY: 0.257 AC XY: 41006 AN XY: 159688

African (AFR) AF: 0.513 AC: 4403 AN: 8584

American (AMR) AF: 0.481 AC: 6659 AN: 13850

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 1524 AN: 8238

East Asian (EAS) AF: 0.445 AC: 7000 AN: 15724

South Asian (SAS) AF: 0.254 AC: 10881 AN: 42922

European-Finnish (FIN) AF: 0.258 AC: 3398 AN: 13186

Middle Eastern (MID) AF: 0.177 AC: 215 AN: 1214

European-Non Finnish (NFE) AF: 0.219 AC: 38438 AN: 175338

Other (OTH) AF: 0.262 AC: 4197 AN: 16036

GnomAD4 genome AF: 0.332 AC: 50533 AN: 152002 Hom.: 9796 Cov.: 32 AF XY: 0.336 AC XY: 24986 AN XY: 74296

African (AFR) AF: 0.509 AC: 21102 AN: 41422

American (AMR) AF: 0.429 AC: 6556 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 677 AN: 3462

East Asian (EAS) AF: 0.418 AC: 2157 AN: 5166

South Asian (SAS) AF: 0.277 AC: 1333 AN: 4816

European-Finnish (FIN) AF: 0.277 AC: 2923 AN: 10548

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14932 AN: 67992

Other (OTH) AF: 0.321 AC: 678 AN: 2114

Alfa AF: 0.262 Hom.: 14442

Bravo AF: 0.355

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	-	Diabetes mellitus type 2, susceptibility to (1)
-	-	-	High density lipoprotein cholesterol level quantitative trait locus 12 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.46
PhyloP100		0.45
PromoterAI		-0.024	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: rs2070895; hg19: chr15-58723939;