21-14152600-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001302998.2(LIPI):c.1091G>A(p.Gly364Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,581,204 control chromosomes in the GnomAD database, including 3,524 homozygotes. In-silico tool predicts 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 0.040 (338 hom., cov: 32)
  • Exomes 𝑓: 0.038 (3186 hom.)
• Consequence: LIPI NM_001302998.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15

Genes affected

LIPI (HGNC:18821): (lipase I) The protein encoded by this gene is a phospholipase that hydrolyzes phosphatidic acid to produce lysophosphatidic acid. Defects in this gene are a cause of susceptibility to familial hypertrigliceridemia. This gene is also expressed at high levels in Ewing family tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005080998).
• BP6: Variant 21-14152600-C-T is Benign according to our data. Variant chr21-14152600-C-T is described in ClinVar as [Benign]. Clinvar id is 1631719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPI	NM_001302998.2	c.1091G>A	p.Gly364Glu	missense_variant	8/10	ENST00000681601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPI	ENST00000681601.1	c.1091G>A	p.Gly364Glu	missense_variant	8/10		NM_001302998.2	P4

Frequencies

GnomAD3 genomes AF: 0.0397 AC: 6033 AN: 151928 Hom.: 338 Cov.: 32

Gnomad AFR AF: 0.00856

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0234

Gnomad OTH AF: 0.0378

GnomAD3 exomes AF: 0.0690 AC: 17120 AN: 248060 Hom.: 1444 AF XY: 0.0647 AC XY: 8683 AN XY: 134254

Gnomad AFR exome AF: 0.00840

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.00731

Gnomad EAS exome AF: 0.274

Gnomad SAS exome AF: 0.0863

Gnomad FIN exome AF: 0.0369

Gnomad NFE exome AF: 0.0213

Gnomad OTH exome AF: 0.0489

GnomAD4 exome AF: 0.0377 AC: 53815 AN: 1429158 Hom.: 3186 Cov.: 27 AF XY: 0.0383 AC XY: 27274 AN XY: 712778

Gnomad4 AFR exome AF: 0.00741

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.00723

Gnomad4 EAS exome AF: 0.288

Gnomad4 SAS exome AF: 0.0857

Gnomad4 FIN exome AF: 0.0388

Gnomad4 NFE exome AF: 0.0213

Gnomad4 OTH exome AF: 0.0405

GnomAD4 genome AF: 0.0397 AC: 6041 AN: 152046 Hom.: 338 Cov.: 32 AF XY: 0.0438 AC XY: 3257 AN XY: 74332

Gnomad4 AFR AF: 0.00856

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0379

Gnomad4 NFE AF: 0.0234

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0334 Hom.: 476

Bravo AF: 0.0432

TwinsUK AF: 0.0229 AC: 85

ALSPAC AF: 0.0208 AC: 80

ESP6500AA AF: 0.00706 AC: 31

ESP6500EA AF: 0.0194 AC: 165

ExAC AF: 0.0630 AC: 7634

Asia WGS AF: 0.178 AC: 614 AN: 3452

EpiCase AF: 0.0200

EpiControl AF: 0.0197

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.12
Cadd	Benign	22
Dann	Uncertain	0.99
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.78	T;T;T
MetaRNN	Benign	0.0051	T;T;T
MetaSVM	Benign	-1.3	T
MutationTaster	Benign	0.99	P;P
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.5	D;.;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.0030	D;.;.
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.22
MPC		0.14
ClinPred		0.018	T
GERP RS		5.2
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs74369337; hg19: chr21-15524921; COSMIC: COSV60707680;