11-66473411-T-C

Position:

• chr11-66473411-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145065.3(PELI3):​c.627T>C​(p.Asp209=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,612,418 control chromosomes in the GnomAD database, including 50,539 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 (5993 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44546 hom.)
• Consequence: PELI3 NM_145065.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

Genes affected

PELI3 (HGNC:30010): (pellino E3 ubiquitin protein ligase family member 3) The protein encoded by this gene is a scaffold protein and an intermediate signaling protein in the innate immune response pathway. The encoded protein helps transmit the immune response signal from Toll-like receptors to IRAK1/TRAF6 complexes. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=0.053 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PELI3	NM_145065.3	c.627T>C	p.Asp209=	synonymous_variant	6/8	ENST00000320740.12	NP_659502.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PELI3	ENST00000320740.12	c.627T>C	p.Asp209=	synonymous_variant	6/8	1	NM_145065.3	ENSP00000322532

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41102 AN: 151986 Hom.: 5982 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.239 AC: 59596 AN: 249160 Hom.: 7722 AF XY: 0.238 AC XY: 32077 AN XY: 134724

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.261

Gnomad SAS exome AF: 0.194

Gnomad FIN exome AF: 0.385

Gnomad NFE exome AF: 0.241

Gnomad OTH exome AF: 0.216

GnomAD4 exome AF: 0.243 AC: 354656 AN: 1460314 Hom.: 44546 Cov.: 33 AF XY: 0.242 AC XY: 175744 AN XY: 726428

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.256

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.271 AC: 41145 AN: 152104 Hom.: 5993 Cov.: 32 AF XY: 0.273 AC XY: 20280 AN XY: 74352

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.221

Alfa AF: 0.236 Hom.: 6888

Bravo AF: 0.258

Asia WGS AF: 0.230 AC: 801 AN: 3478

EpiCase AF: 0.225

EpiControl AF: 0.233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.0
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2277302; hg19: chr11-66240882;