18-49567420-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006033.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPG	NM_006033.4	MANE Select	c.280-22C>T		intron	N/A	NP_006024.1
	LIPG	NM_001308006.2		c.280-22C>T		intron	N/A	NP_001294935.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPG	ENST00000261292.9	TSL:1 MANE Select	c.280-22C>T		intron	N/A	ENSP00000261292.4
	LIPG	ENST00000580036.5	TSL:1	c.280-22C>T		intron	N/A	ENSP00000462420.1
	LIPG	ENST00000427224.6	TSL:2	c.280-22C>T		intron	N/A	ENSP00000387978.2

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

GnomAD2 exomes AF: 0.763 AC: 186875 AN: 244944 AF XY: 0.774

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 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

African (AFR) AF: 0.969 AC: 32368 AN: 33420

American (AMR) AF: 0.569 AC: 25130 AN: 44148

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 22608 AN: 26020

East Asian (EAS) AF: 0.503 AC: 19938 AN: 39600

South Asian (SAS) AF: 0.857 AC: 73426 AN: 85706

European-Finnish (FIN) AF: 0.736 AC: 39170 AN: 53190

Middle Eastern (MID) AF: 0.922 AC: 5311 AN: 5758

European-Non Finnish (NFE) AF: 0.801 AC: 887808 AN: 1108166

Other (OTH) AF: 0.804 AC: 48411 AN: 60188

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

African (AFR) AF: 0.958 AC: 39822 AN: 41566

American (AMR) AF: 0.664 AC: 10142 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3040 AN: 3472

East Asian (EAS) AF: 0.551 AC: 2847 AN: 5168

South Asian (SAS) AF: 0.844 AC: 4070 AN: 4824

European-Finnish (FIN) AF: 0.740 AC: 7817 AN: 10558

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55061 AN: 67984

Other (OTH) AF: 0.843 AC: 1782 AN: 2114

Alfa AF: 0.835 Hom.: 10879

Bravo AF: 0.821

Asia WGS AF: 0.728 AC: 2531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		-1.3
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: rs2000812; hg19: chr18-47093790; COSMIC: COSV54294901;