21-14178114-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001302998.2(LIPI):c.643+3644A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,094 control chromosomes in the GnomAD database, including 2,761 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 0.17 (2761 hom., cov: 32)
• Consequence: LIPI NM_001302998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPI	NM_001302998.2	c.643+3644A>G		intron_variant		ENST00000681601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPI	ENST00000681601.1	c.643+3644A>G		intron_variant			NM_001302998.2	P4

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26596 AN: 151976 Hom.: 2761 Cov.: 32

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.149

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26607 AN: 152094 Hom.: 2761 Cov.: 32 AF XY: 0.176 AC XY: 13090 AN XY: 74344

Gnomad4 AFR AF: 0.0770

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.154

Alfa AF: 0.206 Hom.: 4422

Bravo AF: 0.160

Asia WGS AF: 0.277 AC: 964 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.6
Dann	Benign	0.73

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: rs374916; hg19: chr21-15550435; COSMIC: COSV60715666;