rs61729804

Variant names:

• chr18-49565437-C-T
• rs61729804
• NM_006033.4:c.218C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-49565437-C-T
• chr18-49565437-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006033.4(LIPG):​c.218C>T​(p.Pro73Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P73S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: LIPG NM_006033.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00900
• Publications: 5 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00712803).
• BP6: Variant 18-49565437-C-T is Benign according to our data. Variant chr18-49565437-C-T is described in ClinVar as Benign. ClinVar VariationId is 1607238.Status of the report is criteria_provided_single_submitter, 1 stars.

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.218C>T	p.Pro73Leu	missense	Exon 2 of 10	NP_006024.1	Q9Y5X9-1
	LIPG	NM_001308006.2		c.218C>T	p.Pro73Leu	missense	Exon 2 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.218C>T	p.Pro73Leu	missense	Exon 2 of 10	ENSP00000261292.4	Q9Y5X9-1
	LIPG	ENST00000580036.5	TSL:1	c.218C>T	p.Pro73Leu	missense	Exon 2 of 6	ENSP00000462420.1	Q9Y5X9-2
	LIPG	ENST00000959465.1		c.218C>T	p.Pro73Leu	missense	Exon 2 of 10	ENSP00000629524.1

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 221 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

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: 0.000957

GnomAD2 exomes AF: 0.000330 AC: 83 AN: 251492 AF XY: 0.000228

Gnomad AFR exome AF: 0.00443

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000122 AC: 179 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.0000935 AC XY: 68 AN XY: 727248

African (AFR) AF: 0.00448 AC: 150 AN: 33480

American (AMR) AF: 0.000291 AC: 13 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.000182 AC: 11 AN: 60396

GnomAD4 genome AF: 0.00145 AC: 221 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.00142 AC XY: 106 AN XY: 74468

African (AFR) AF: 0.00503 AC: 209 AN: 41578

American (AMR) AF: 0.000654 AC: 10 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000366 Hom.: 0

Bravo AF: 0.00175

ESP6500AA AF: 0.00545 AC: 24

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000387 AC: 47

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	0.71
DANN	Benign	0.77
DEOGEN2	Benign	0.28	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.0071	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.0090
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.38	N
REVEL	Uncertain	0.55
Sift	Benign	0.11	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.71
MPC		0.36
ClinPred		0.0019	T
GERP RS		-1.5
Varity_R		0.068
gMVP		0.33
Mutation Taster		=17/83	disease causing

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: rs61729804; hg19: chr18-47091807;