rs11570897

Variant names:

• chr8-19953304-C-T
• rs11570897
• NM_000237.3:c.430-6C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-19953304-C-T
• chr8-19953304-C-A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_000237.3(LPL):​c.430-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,576,400 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (16 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (57 hom.)
• Consequence: LPL NM_000237.3 splice_region, intron
• Scores: Splicing: ADA: 0.001226
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.395
• Publications: 1 publications found

Genes affected

LPL (HGNC:6677): (lipoprotein lipase) LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]

LPL Gene-Disease associations (from GenCC):

• familial lipoprotein lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, Ambry Genetics
• hyperlipidemia, familial combined, LPL related

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 8-19953304-C-T is Benign according to our data. Variant chr8-19953304-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 362408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00459 (699/152204) while in subpopulation AMR AF = 0.034 (520/15288). AF 95% confidence interval is 0.0316. There are 16 homozygotes in GnomAd4. There are 419 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000237.3. 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
	LPL	NM_000237.3	MANE Select	c.430-6C>T		splice_region intron	N/A	NP_000228.1	P06858

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.430-6C>T		splice_region intron	N/A	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.430-6C>T		splice_region intron	N/A	ENSP00000635987.1
	LPL	ENST00000965929.1		c.430-9C>T		intron	N/A	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.00456 AC: 694 AN: 152086 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00827

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00595

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00789 AC: 1983 AN: 251344 AF XY: 0.00614

Gnomad AFR exome AF: 0.000738

Gnomad AMR exome AF: 0.0480

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00386

Gnomad FIN exome AF: 0.00753

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00221 AC: 3143 AN: 1424196 Hom.: 57 Cov.: 25 AF XY: 0.00196 AC XY: 1396 AN XY: 710946

African (AFR) AF: 0.000398 AC: 13 AN: 32682

American (AMR) AF: 0.0461 AC: 2061 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25882

East Asian (EAS) AF: 0.0101 AC: 398 AN: 39462

South Asian (SAS) AF: 0.000351 AC: 30 AN: 85576

European-Finnish (FIN) AF: 0.00714 AC: 381 AN: 53360

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5708

European-Non Finnish (NFE) AF: 0.000121 AC: 130 AN: 1077852

Other (OTH) AF: 0.00219 AC: 129 AN: 59000

GnomAD4 genome AF: 0.00459 AC: 699 AN: 152204 Hom.: 16 Cov.: 33 AF XY: 0.00563 AC XY: 419 AN XY: 74414

African (AFR) AF: 0.000722 AC: 30 AN: 41526

American (AMR) AF: 0.0340 AC: 520 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00829 AC: 43 AN: 5190

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.00595 AC: 63 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68004

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00364 Hom.: 9

Bravo AF: 0.00628

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)
-	-	1	Hyperlipoproteinemia, type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	8.8
DANN	Benign	0.80
PhyloP100		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.034
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: rs11570897; hg19: chr8-19810815;