rs253

Variant names:

• chr8-19953906-C-T
• rs253
• NM_000237.3:c.542-214C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-19953906-C-T
• chr8-19953906-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000237.3(LPL):​c.542-214C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,066 control chromosomes in the GnomAD database, including 22,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (22085 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850
• Publications: 32 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-19953906-C-T is Benign according to our data. Variant chr8-19953906-C-T is described in ClinVar as Benign. ClinVar VariationId is 1248743.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

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.542-214C>T		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.542-214C>T		intron	N/A	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.542-214C>T		intron	N/A	ENSP00000635987.1
	LPL	ENST00000965929.1		c.539-214C>T		intron	N/A	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79363 AN: 151948 Hom.: 22051 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.474

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.522 AC: 79441 AN: 152066 Hom.: 22085 Cov.: 32 AF XY: 0.517 AC XY: 38413 AN XY: 74310

African (AFR) AF: 0.723 AC: 30010 AN: 41498

American (AMR) AF: 0.456 AC: 6971 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1414 AN: 3468

East Asian (EAS) AF: 0.347 AC: 1790 AN: 5162

South Asian (SAS) AF: 0.406 AC: 1958 AN: 4824

European-Finnish (FIN) AF: 0.450 AC: 4754 AN: 10562

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 31009 AN: 67958

Other (OTH) AF: 0.472 AC: 996 AN: 2112

Alfa AF: 0.471 Hom.: 29919

Bravo AF: 0.526

Asia WGS AF: 0.391 AC: 1360 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		-0.085

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: rs253; hg19: chr8-19811417;