NM_006033.4:c.1377-108C>T

Variant names:

• chr18-49586638-C-T
• rs6507931
• NM_006033.4:c.1377-108C>T

Variant summary

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

The NM_006033.4(LIPG):​c.1377-108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 775,888 control chromosomes in the GnomAD database, including 112,500 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 0.52 (20992 hom., cov: 31)
  • Exomes 𝑓: 0.53 (91508 hom.)
• Consequence: LIPG NM_006033.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 14 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPG	NM_006033.4	MANE Select	c.1377-108C>T		intron	N/A	NP_006024.1
	LIPG	NM_001308006.2		c.1155-108C>T		intron	N/A	NP_001294935.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPG	ENST00000261292.9	TSL:1 MANE Select	c.1377-108C>T		intron	N/A	ENSP00000261292.4
	LIPG	ENST00000427224.6	TSL:2	c.1155-108C>T		intron	N/A	ENSP00000387978.2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78666 AN: 151862 Hom.: 20984 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.528 AC: 329252 AN: 623906 Hom.: 91508 AF XY: 0.538 AC XY: 180554 AN XY: 335706

African (AFR) AF: 0.501 AC: 8845 AN: 17672

American (AMR) AF: 0.450 AC: 16371 AN: 36364

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 11268 AN: 20118

East Asian (EAS) AF: 0.111 AC: 3822 AN: 34570

South Asian (SAS) AF: 0.648 AC: 42582 AN: 65678

European-Finnish (FIN) AF: 0.433 AC: 21232 AN: 49090

Middle Eastern (MID) AF: 0.725 AC: 2922 AN: 4030

European-Non Finnish (NFE) AF: 0.564 AC: 205045 AN: 363846

Other (OTH) AF: 0.528 AC: 17165 AN: 32538

GnomAD4 genome AF: 0.518 AC: 78703 AN: 151982 Hom.: 20992 Cov.: 31 AF XY: 0.512 AC XY: 38042 AN XY: 74268

African (AFR) AF: 0.497 AC: 20591 AN: 41432

American (AMR) AF: 0.491 AC: 7501 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1945 AN: 3468

East Asian (EAS) AF: 0.141 AC: 727 AN: 5172

South Asian (SAS) AF: 0.634 AC: 3054 AN: 4820

European-Finnish (FIN) AF: 0.419 AC: 4424 AN: 10550

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38480 AN: 67944

Other (OTH) AF: 0.542 AC: 1142 AN: 2106

Alfa AF: 0.546 Hom.: 22909

Bravo AF: 0.517

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.31
DANN	Benign	0.29
PhyloP100		-1.7
Mutation Taster		=100/0	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: rs6507931; hg19: chr18-47113008; COSMIC: COSV107205082; COSMIC: COSV107205082;