21-14163413-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001302998.2(LIPI):c.1006+6T>A variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.000285 in 1,277,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: LIPI NM_001302998.2 splice_donor_region, intron
• Scores: Splicing: ADA: 0.9331
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.25

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 21-14163413-A-T is Benign according to our data. Variant chr21-14163413-A-T is described in ClinVar as [Benign]. Clinvar id is 2071599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 242 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPI	NM_001302998.2	c.1006+6T>A		splice_donor_region_variant, intron_variant		ENST00000681601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPI	ENST00000681601.1	c.1006+6T>A		splice_donor_region_variant, intron_variant			NM_001302998.2	P4

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 242 AN: 152010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000353 AC: 88 AN: 249460 Hom.: 0 AF XY: 0.000230 AC XY: 31 AN XY: 134830

Gnomad AFR exome AF: 0.00520

Gnomad AMR exome AF: 0.0000876

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000108 AC: 122 AN: 1125086 Hom.: 0 Cov.: 16 AF XY: 0.0000903 AC XY: 52 AN XY: 575900

Gnomad4 AFR exome AF: 0.00410

Gnomad4 AMR exome AF: 0.000136

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000122

GnomAD4 genome AF: 0.00159 AC: 242 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.00157 AC XY: 117 AN XY: 74374

Gnomad4 AFR AF: 0.00571

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000402 Hom.: 0

Bravo AF: 0.00173

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

Jun 29, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	16
Dann	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.93
dbscSNV1_RF	Benign	0.65
SpliceAI score (max)		0.59		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.59		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs189893165; hg19: chr21-15535734;