chr2-64100410-G-T

Position:

• chr2-64100410-G-T

Variant summary

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

The ENST00000358912.5(PELI1):​c.291C>A​(p.Thr97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,468,306 control chromosomes in the GnomAD database, including 69,147 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 0.28 (6905 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62242 hom.)
• Consequence: PELI1 ENST00000358912.5 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=-0.41).
• BP7: Synonymous conserved (PhyloP=-0.117 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PELI1	NM_020651.4	c.291C>A	p.Thr97=	synonymous_variant	4/7	ENST00000358912.5	NP_065702.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PELI1	ENST00000358912.5	c.291C>A	p.Thr97=	synonymous_variant	4/7	1	NM_020651.4	ENSP00000351789	P1
PELI1	ENST00000466177.6	n.686C>A		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41665 AN: 151494 Hom.: 6888 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.281

GnomAD3 exomes AF: 0.341 AC: 85319 AN: 249868 Hom.: 16837 AF XY: 0.341 AC XY: 46016 AN XY: 135112

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.306

Gnomad EAS exome AF: 0.740

Gnomad SAS exome AF: 0.354

Gnomad FIN exome AF: 0.276

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.294 AC: 387004 AN: 1316696 Hom.: 62242 Cov.: 22 AF XY: 0.297 AC XY: 196903 AN XY: 662582

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.295

Gnomad4 EAS exome AF: 0.746

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.282

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.275 AC: 41707 AN: 151610 Hom.: 6905 Cov.: 32 AF XY: 0.278 AC XY: 20574 AN XY: 74088

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.289

Alfa AF: 0.260 Hom.: 2610

Bravo AF: 0.276

Asia WGS AF: 0.544 AC: 1889 AN: 3476

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	-0.41
CADD	Benign	6.5
DANN	Benign	0.70
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: rs329498; hg19: chr2-64327544; COSMIC: COSV62730620;