rs2000813

Variant names:

• chr18-49567494-C-T
• rs2000813
• NM_006033.4:c.332C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-49567494-C-T
• chr18-49567494-C-A
• chr18-49567494-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006033.4(LIPG):​c.332C>T​(p.Thr111Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,613,700 control chromosomes in the GnomAD database, including 67,329 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4746 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62583 hom.)
• Consequence: LIPG NM_006033.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.421
• Publications: 109 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012551069).
• BP6: Variant 18-49567494-C-T is Benign according to our data. Variant chr18-49567494-C-T is described in ClinVar as Benign. ClinVar VariationId is 1647588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006033.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPG	NM_006033.4	MANE Select	c.332C>T	p.Thr111Ile	missense	Exon 3 of 10	NP_006024.1	Q9Y5X9-1
	LIPG	NM_001308006.2		c.332C>T	p.Thr111Ile	missense	Exon 3 of 9	NP_001294935.1	B4DTR8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPG	ENST00000261292.9	TSL:1 MANE Select	c.332C>T	p.Thr111Ile	missense	Exon 3 of 10	ENSP00000261292.4	Q9Y5X9-1
	LIPG	ENST00000580036.5	TSL:1	c.332C>T	p.Thr111Ile	missense	Exon 3 of 6	ENSP00000462420.1	Q9Y5X9-2
	LIPG	ENST00000959465.1		c.332C>T	p.Thr111Ile	missense	Exon 3 of 10	ENSP00000629524.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35434 AN: 152006 Hom.: 4752 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.279

GnomAD2 exomes AF: 0.266 AC: 66755 AN: 251106 AF XY: 0.276

Gnomad AFR exome AF: 0.0943

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.330

Gnomad FIN exome AF: 0.277

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.290

GnomAD4 exome AF: 0.288 AC: 421079 AN: 1461576 Hom.: 62583 Cov.: 37 AF XY: 0.290 AC XY: 211173 AN XY: 727098

African (AFR) AF: 0.0939 AC: 3142 AN: 33472

American (AMR) AF: 0.162 AC: 7258 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 7322 AN: 26126

East Asian (EAS) AF: 0.285 AC: 11309 AN: 39690

South Asian (SAS) AF: 0.304 AC: 26211 AN: 86240

European-Finnish (FIN) AF: 0.281 AC: 14997 AN: 53412

Middle Eastern (MID) AF: 0.363 AC: 2093 AN: 5768

European-Non Finnish (NFE) AF: 0.298 AC: 331347 AN: 1111768

Other (OTH) AF: 0.288 AC: 17400 AN: 60388

GnomAD4 genome AF: 0.233 AC: 35410 AN: 152124 Hom.: 4746 Cov.: 32 AF XY: 0.233 AC XY: 17350 AN XY: 74352

African (AFR) AF: 0.0989 AC: 4106 AN: 41532

American (AMR) AF: 0.215 AC: 3292 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 963 AN: 3470

East Asian (EAS) AF: 0.318 AC: 1644 AN: 5170

South Asian (SAS) AF: 0.306 AC: 1474 AN: 4824

European-Finnish (FIN) AF: 0.272 AC: 2870 AN: 10552

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20071 AN: 67986

Other (OTH) AF: 0.276 AC: 581 AN: 2106

Alfa AF: 0.278 Hom.: 30546

Bravo AF: 0.223

TwinsUK AF: 0.291 AC: 1079

ALSPAC AF: 0.298 AC: 1149

ESP6500AA AF: 0.107 AC: 473

ESP6500EA AF: 0.291 AC: 2506

ExAC AF: 0.267 AC: 32367

Asia WGS AF: 0.248 AC: 860 AN: 3478

EpiCase AF: 0.313

EpiControl AF: 0.312

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	2.3
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.78	N
PhyloP100		0.42
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.20
Sift	Benign	0.070	T
Sift4G	Benign	0.24	T
Polyphen		0.0030	B
Vest4		0.14
MPC		0.39
ClinPred		0.0038	T
GERP RS		-3.6
Varity_R		0.037
gMVP		0.15
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2000813; hg19: chr18-47093864; COSMIC: COSV54294912; COSMIC: COSV54294912;