21-14109044-G-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.1332C>A(p.Asp444Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,593,002 control chromosomes in the GnomAD database, including 202,725 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D444V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.51 (19642 hom., cov: 32)
  • Exomes 𝑓: 0.50 (183083 hom.)
• Consequence: LIPI NM_001302998.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.208

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.8838337E-5).
• BP6: Variant 21-14109044-G-T is Benign according to our data. Variant chr21-14109044-G-T is described in ClinVar as [Benign]. Clinvar id is 1600119.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPI	NM_001302998.2	c.1332C>A	p.Asp444Glu	missense_variant	10/10	ENST00000681601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPI	ENST00000681601.1	c.1332C>A	p.Asp444Glu	missense_variant	10/10		NM_001302998.2	P4
	ENST00000428809.5	n.372+24900G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77080 AN: 151660 Hom.: 19595 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.507

GnomAD3 exomes AF: 0.502 AC: 125854 AN: 250826 Hom.: 31851 AF XY: 0.501 AC XY: 67931 AN XY: 135590

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.492

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.520

Gnomad SAS exome AF: 0.531

Gnomad FIN exome AF: 0.521

Gnomad NFE exome AF: 0.496

Gnomad OTH exome AF: 0.486

GnomAD4 exome AF: 0.503 AC: 724318 AN: 1441222 Hom.: 183083 Cov.: 29 AF XY: 0.502 AC XY: 360697 AN XY: 718344

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.441

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.523

Gnomad4 FIN exome AF: 0.515

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome AF: 0.508 AC: 77179 AN: 151780 Hom.: 19642 Cov.: 32 AF XY: 0.509 AC XY: 37740 AN XY: 74146

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.513

Alfa AF: 0.498 Hom.: 43927

Bravo AF: 0.505

TwinsUK AF: 0.500 AC: 1855

ALSPAC AF: 0.523 AC: 2017

ESP6500AA AF: 0.508 AC: 2238

ESP6500EA AF: 0.494 AC: 4250

ExAC AF: 0.501 AC: 60797

Asia WGS AF: 0.550 AC: 1913 AN: 3474

EpiCase AF: 0.485

EpiControl AF: 0.488

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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	2.5
Dann	Benign	0.70
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00060	N
LIST_S2	Benign	0.19	T;T;T
MetaRNN	Benign	0.000059	T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	2.2	N;.;.
REVEL	Benign	0.23
Sift	Benign	1.0	T;.;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.049
MutPred		0.43		Gain of sheet (P = 0.0125);.;.;
MPC		0.017
ClinPred		0.0020	T
GERP RS		0.13
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs7278737; hg19: chr21-15481365; COSMIC: COSV60707898;