rs34474737

Variant names:

• chr18-49562285-T-G
• rs34474737
• NM_006033.4:c.-24T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006033.4(LIPG):​c.-24T>G variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6245 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77405 hom.)
• Consequence: LIPG NM_006033.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 20 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=-0.77).
• 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 rank	MANE	Protein	UniProt
LIPG	NM_006033.4	c.-24T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 10	ENST00000261292.9	NP_006024.1
LIPG	NM_006033.4	c.-24T>G		5_prime_UTR_variant	Exon 1 of 10	ENST00000261292.9	NP_006024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9	c.-24T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 10	1	NM_006033.4	ENSP00000261292.4
LIPG	ENST00000261292.9	c.-24T>G		5_prime_UTR_variant	Exon 1 of 10	1	NM_006033.4	ENSP00000261292.4

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

GnomAD2 exomes AF: 0.296 AC: 73846 AN: 249770 AF XY: 0.305

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 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

African (AFR) AF: 0.167 AC: 5583 AN: 33418

American (AMR) AF: 0.178 AC: 7959 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7521 AN: 26134

East Asian (EAS) AF: 0.292 AC: 11589 AN: 39696

South Asian (SAS) AF: 0.317 AC: 27324 AN: 86166

European-Finnish (FIN) AF: 0.308 AC: 16441 AN: 53384

Middle Eastern (MID) AF: 0.395 AC: 1795 AN: 4540

European-Non Finnish (NFE) AF: 0.335 AC: 372060 AN: 1111904

Other (OTH) AF: 0.323 AC: 19482 AN: 60270

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

African (AFR) AF: 0.172 AC: 7141 AN: 41506

American (AMR) AF: 0.236 AC: 3605 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1691 AN: 5176

South Asian (SAS) AF: 0.313 AC: 1504 AN: 4812

European-Finnish (FIN) AF: 0.293 AC: 3104 AN: 10578

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22774 AN: 67982

Other (OTH) AF: 0.329 AC: 693 AN: 2108

Alfa AF: 0.299 Hom.: 2041

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
PhyloP100		-0.17
PromoterAI		-0.034	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34474737; hg19: chr18-47088655; COSMIC: COSV54295085; COSMIC: COSV54295085;