chr18-49567426-C-G

Position:

• chr18-49567426-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_006033.4(LIPG):​c.280-16C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,612,628 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (14 hom.)
• Consequence: LIPG NM_006033.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.201

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-49567426-C-G is Benign according to our data. Variant chr18-49567426-C-G is described in ClinVar as [Benign]. Clinvar id is 1603010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49567426-C-G is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPG	NM_006033.4	c.280-16C>G		intron_variant		ENST00000261292.9	NP_006024.1
LIPG	NM_001308006.2	c.280-16C>G		intron_variant			NP_001294935.1
LIPG	XM_047437944.1	c.388-16C>G		intron_variant			XP_047293900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9	c.280-16C>G		intron_variant		1	NM_006033.4	ENSP00000261292.4

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 320 AN: 152176 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00499

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00299 AC: 744 AN: 248906 Hom.: 3 AF XY: 0.00343 AC XY: 461 AN XY: 134506

Gnomad AFR exome AF: 0.000438

Gnomad AMR exome AF: 0.000902

Gnomad ASJ exome AF: 0.0204

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00521

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00277

Gnomad OTH exome AF: 0.00541

GnomAD4 exome AF: 0.00278 AC: 4054 AN: 1460334 Hom.: 14 Cov.: 33 AF XY: 0.00294 AC XY: 2134 AN XY: 726336

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.0192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00552

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.00245

Gnomad4 OTH exome AF: 0.00383

GnomAD4 genome AF: 0.00209 AC: 319 AN: 152294 Hom.: 1 Cov.: 33 AF XY: 0.00216 AC XY: 161 AN XY: 74446

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00499

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00276

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00494 Hom.: 0

Bravo AF: 0.00221

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.9
DANN	Benign	0.57

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: rs201857867; hg19: chr18-47093796;