chr18-49562384-G-A

Position:

• chr18-49562384-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006033.4(LIPG):​c.76G>A​(p.Gly26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,613,942 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.014 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (44 hom.)
• Consequence: LIPG NM_006033.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.63

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027477443).
• BP6: Variant 18-49562384-G-A is Benign according to our data. Variant chr18-49562384-G-A is described in ClinVar as [Benign]. Clinvar id is 1169605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49562384-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2177/152220) while in subpopulation AFR AF= 0.0505 (2095/41516). AF 95% confidence interval is 0.0487. There are 60 homozygotes in gnomad4. There are 987 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPG	NM_006033.4	c.76G>A	p.Gly26Ser	missense_variant	1/10	ENST00000261292.9	NP_006024.1
LIPG	NM_001308006.2	c.76G>A	p.Gly26Ser	missense_variant	1/9		NP_001294935.1
LIPG	XM_047437944.1	c.205+494G>A		intron_variant			XP_047293900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9	c.76G>A	p.Gly26Ser	missense_variant	1/10	1	NM_006033.4	ENSP00000261292.4

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2178 AN: 152102 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

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: 0.0000882

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00365 AC: 909 AN: 249286 Hom.: 12 AF XY: 0.00255 AC XY: 344 AN XY: 134928

Gnomad AFR exome AF: 0.0522

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000717

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00141 AC: 2057 AN: 1461722 Hom.: 44 Cov.: 34 AF XY: 0.00121 AC XY: 883 AN XY: 727148

Gnomad4 AFR exome AF: 0.0507

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.00348

GnomAD4 genome AF: 0.0143 AC: 2177 AN: 152220 Hom.: 60 Cov.: 32 AF XY: 0.0133 AC XY: 987 AN XY: 74412

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.00418

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00272 Hom.: 22

Bravo AF: 0.0163

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0463 AC: 204

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00478 AC: 580

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.83
DEOGEN2	Benign	0.051	T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.63	T;T;T
MetaRNN	Benign	0.0027	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L;.;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.34	N;N;.
REVEL	Benign	0.24
Sift	Benign	0.26	T;T;.
Sift4G	Benign	0.49	T;T;T
Polyphen		0.029	B;B;B
Vest4		0.075
MVP		0.91
MPC		0.36
ClinPred		0.0058	T
GERP RS		2.4
Varity_R		0.077
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs9963243; hg19: chr18-47088754;