18-49567420-C-T

Variant names:

• chr18-49567420-C-T
• rs2000812
• NM_006033.4:c.280-22C>T

Variant summary

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

The NM_006033.4(LIPG):​c.280-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,608,356 control chromosomes in the GnomAD database, including 514,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.83 (52783 hom., cov: 32)
  • Exomes 𝑓: 0.79 (462125 hom.)
• Consequence: LIPG NM_006033.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.96).
• BP6: Variant 18-49567420-C-T is Benign according to our data. Variant chr18-49567420-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPG	NM_006033.4	c.280-22C>T		intron_variant	Intron 2 of 9	ENST00000261292.9	NP_006024.1
LIPG	NM_001308006.2	c.280-22C>T		intron_variant	Intron 2 of 8		NP_001294935.1
LIPG	XM_047437944.1	c.388-22C>T		intron_variant	Intron 2 of 4		XP_047293900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9	c.280-22C>T		intron_variant	Intron 2 of 9	1	NM_006033.4	ENSP00000261292.4

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125519 AN: 152042 Hom.: 52729 Cov.: 32

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.841

GnomAD3 exomes AF: 0.763 AC: 186875 AN: 244944 Hom.: 73246 AF XY: 0.774 AC XY: 102458 AN XY: 132326

Gnomad AFR exome AF: 0.963

Gnomad AMR exome AF: 0.559

Gnomad ASJ exome AF: 0.869

Gnomad EAS exome AF: 0.554

Gnomad SAS exome AF: 0.857

Gnomad FIN exome AF: 0.737

Gnomad NFE exome AF: 0.800

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.793 AC: 1154170 AN: 1456196 Hom.: 462125 Cov.: 33 AF XY: 0.796 AC XY: 576792 AN XY: 724206

Gnomad4 AFR exome AF: 0.969

Gnomad4 AMR exome AF: 0.569

Gnomad4 ASJ exome AF: 0.869

Gnomad4 EAS exome AF: 0.503

Gnomad4 SAS exome AF: 0.857

Gnomad4 FIN exome AF: 0.736

Gnomad4 NFE exome AF: 0.801

Gnomad4 OTH exome AF: 0.804

GnomAD4 genome AF: 0.826 AC: 125623 AN: 152160 Hom.: 52783 Cov.: 32 AF XY: 0.820 AC XY: 60974 AN XY: 74358

Gnomad4 AFR AF: 0.958

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.843

Alfa AF: 0.832 Hom.: 10526

Bravo AF: 0.821

Asia WGS AF: 0.728 AC: 2531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.5
DANN	Benign	0.58

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: rs2000812; hg19: chr18-47093790; COSMIC: COSV54294901;