18-49562285-T-G

Position:

• chr18-49562285-T-G

Variant summary

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

The NM_006033.4(LIPG):​c.-24T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,612,364 control chromosomes in the GnomAD database, including 83,650 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (6245 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77405 hom.)
• Consequence: LIPG NM_006033.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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=-0.77).
• BP6: Variant 18-49562285-T-G is Benign according to our data. Variant chr18-49562285-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPG	NM_006033.4	c.-24T>G		5_prime_UTR_variant	1/10	ENST00000261292.9
LIPG	NM_001308006.2	c.-24T>G		5_prime_UTR_variant	1/9
LIPG	XM_047437944.1	c.205+395T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPG	ENST00000261292.9	c.-24T>G		5_prime_UTR_variant	1/10	1	NM_006033.4	P1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41955 AN: 152016 Hom.: 6254 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.296 AC: 73846 AN: 249770 Hom.: 11640 AF XY: 0.305 AC XY: 41246 AN XY: 135224

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.337

Gnomad SAS exome AF: 0.316

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.321

GnomAD4 exome AF: 0.322 AC: 469754 AN: 1460230 Hom.: 77405 Cov.: 40 AF XY: 0.324 AC XY: 235154 AN XY: 726396

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.335

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.276 AC: 41941 AN: 152134 Hom.: 6245 Cov.: 32 AF XY: 0.274 AC XY: 20396 AN XY: 74348

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.329

Alfa AF: 0.302 Hom.: 2032

Bravo AF: 0.268

Asia WGS AF: 0.264 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34474737; hg19: chr18-47088655; COSMIC: COSV54295085; COSMIC: COSV54295085;