21-14109087-AAG-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001302998.2(LIPI):c.1296-9_1296-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,587,642 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: LIPI NM_001302998.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.366

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 21-14109087-AAG-A is Benign according to our data. Variant chr21-14109087-AAG-A is described in ClinVar as [Benign]. Clinvar id is 1656832.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPI	NM_001302998.2	c.1296-9_1296-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000681601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPI	ENST00000681601.1	c.1296-9_1296-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001302998.2	P4
	ENST00000428809.5	n.372+24947_372+24948del		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00807

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000696 AC: 174 AN: 250100 Hom.: 0 AF XY: 0.000658 AC XY: 89 AN XY: 135248

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00935

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000216 AC: 310 AN: 1435404 Hom.: 1 AF XY: 0.000222 AC XY: 159 AN XY: 715614

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00753

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000276

Gnomad4 OTH exome AF: 0.000151

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26 AN XY: 74436

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00809

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000287

Asia WGS AF: 0.00116 AC: 5 AN: 3474

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

Jul 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs375881555; hg19: chr21-15481408;