rs2276269

Positions:

• chr18-49575632-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_006033.4(LIPG):​c.793+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,533,108 control chromosomes in the GnomAD database, including 255,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.61 (29703 hom., cov: 30)
  • Exomes 𝑓: 0.57 (225483 hom.)
• Consequence: LIPG NM_006033.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

Genes affected

LIPG (HGNC:6623): (lipase G, endothelial type) The protein encoded by this gene has substantial phospholipase activity and may be involved in lipoprotein metabolism and vascular biology. This protein is designated a member of the TG lipase family by its sequence and characteristic lid region which provides substrate specificity for enzymes of the TG lipase family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-49575632-T-C is Benign according to our data. Variant chr18-49575632-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPG	NM_006033.4	c.793+42T>C		intron_variant		ENST00000261292.9	NP_006024.1
LIPG	NM_001308006.2	c.572-5783T>C		intron_variant			NP_001294935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9	c.793+42T>C		intron_variant		1	NM_006033.4	ENSP00000261292.4
LIPG	ENST00000580036.5	c.793+42T>C		intron_variant		1		ENSP00000462420.1
LIPG	ENST00000427224.6	c.572-5783T>C		intron_variant		2		ENSP00000387978.2
LIPG	ENST00000577628.5	c.901+42T>C		intron_variant		2		ENSP00000463835.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92509 AN: 151836 Hom.: 29669 Cov.: 30

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.622

GnomAD3 exomes AF: 0.547 AC: 126752 AN: 231804 Hom.: 36272 AF XY: 0.558 AC XY: 70033 AN XY: 125576

Gnomad AFR exome AF: 0.813

Gnomad AMR exome AF: 0.368

Gnomad ASJ exome AF: 0.573

Gnomad EAS exome AF: 0.358

Gnomad SAS exome AF: 0.685

Gnomad FIN exome AF: 0.440

Gnomad NFE exome AF: 0.571

Gnomad OTH exome AF: 0.541

GnomAD4 exome AF: 0.565 AC: 780433 AN: 1381154 Hom.: 225483 Cov.: 20 AF XY: 0.570 AC XY: 393666 AN XY: 690540

Gnomad4 AFR exome AF: 0.821

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.565

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.682

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.609 AC: 92591 AN: 151954 Hom.: 29703 Cov.: 30 AF XY: 0.600 AC XY: 44567 AN XY: 74278

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.622

Alfa AF: 0.583 Hom.: 35464

Bravo AF: 0.615

Asia WGS AF: 0.499 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.54
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs2276269; hg19: chr18-47102002; COSMIC: COSV54294757;