rs874566

Variant names:

• chr18-49562371-C-G
• rs874566
• NM_006033.4:c.63C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-49562371-C-G
• chr18-49562371-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006033.4(LIPG):​c.63C>G​(p.Ser21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S21S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LIPG NM_006033.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19638804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPG	NM_006033.4	c.63C>G	p.Ser21Arg	missense_variant	Exon 1 of 10	ENST00000261292.9	NP_006024.1
LIPG	NM_001308006.2	c.63C>G	p.Ser21Arg	missense_variant	Exon 1 of 9		NP_001294935.1
LIPG	XM_047437944.1	c.205+481C>G		intron_variant	Intron 1 of 4		XP_047293900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9	c.63C>G	p.Ser21Arg	missense_variant	Exon 1 of 10	1	NM_006033.4	ENSP00000261292.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152038 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152038 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74252

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.095	T;T;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.69	T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.90	L;.;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N;N;.
REVEL	Uncertain	0.34
Sift	Benign	0.054	T;D;.
Sift4G	Benign	0.21	T;T;T
Polyphen		0.21	B;B;B
Vest4		0.32
MutPred		0.51		Loss of catalytic residue at S21 (P = 0.0553);Loss of catalytic residue at S21 (P = 0.0553);Loss of catalytic residue at S21 (P = 0.0553);
MVP		0.95
MPC		0.54
ClinPred		0.13	T
GERP RS		2.6
Varity_R		0.093
gMVP		0.33

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: rs874566; hg19: chr18-47088741;