rs329497

chr2-64100458-T-Cchr2-64100458-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_020651.4(PELI1):c.243A>G(p.Leu81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,563,734 control chromosomes in the GnomAD database, including 80,808 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 0.27 (6815 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73993 hom.)
• Consequence: PELI1 NM_020651.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

Genes affected

PELI1 (HGNC:8827): (pellino E3 ubiquitin protein ligase 1) Enables ubiquitin protein ligase activity. Involved in several processes, including negative regulation of necroptotic process; protein polyubiquitination; and response to lipopolysaccharide. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=0.117 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PELI1	NM_020651.4	c.243A>G	p.Leu81=	synonymous_variant	4/7	ENST00000358912.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PELI1	ENST00000358912.5	c.243A>G	p.Leu81=	synonymous_variant	4/7	1	NM_020651.4	P1
PELI1	ENST00000466177.6	n.638A>G		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40991 AN: 151928 Hom.: 6797 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.278

GnomAD3 exomes AF: 0.342 AC: 85781 AN: 251016 Hom.: 16989 AF XY: 0.341 AC XY: 46272 AN XY: 135668

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.740

Gnomad SAS exome AF: 0.355

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.308 AC: 434670 AN: 1411688 Hom.: 73993 Cov.: 28 AF XY: 0.310 AC XY: 218469 AN XY: 705120

Gnomad4 AFR exome AF: 0.0968

Gnomad4 AMR exome AF: 0.385

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.311

GnomAD4 genome AF: 0.270 AC: 41028 AN: 152046 Hom.: 6815 Cov.: 32 AF XY: 0.273 AC XY: 20259 AN XY: 74312

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.286

Alfa AF: 0.298 Hom.: 11220

Bravo AF: 0.270

Asia WGS AF: 0.543 AC: 1885 AN: 3474

EpiCase AF: 0.305

EpiControl AF: 0.305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	6.6
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs329497; hg19: chr2-64327592; COSMIC: COSV62729818;