2-64100410-G-C

Variant names:

• chr2-64100410-G-C
• rs329498
• NM_020651.4:c.291C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_020651.4(PELI1):​c.291C>G​(p.Thr97Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PELI1 NM_020651.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 21 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=-0.117 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020651.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PELI1	NM_020651.4	MANE Select	c.291C>G	p.Thr97Thr	synonymous	Exon 4 of 7	NP_065702.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PELI1	ENST00000358912.5	TSL:1 MANE Select	c.291C>G	p.Thr97Thr	synonymous	Exon 4 of 7	ENSP00000351789.4	Q96FA3
	PELI1	ENST00000903228.1		c.360C>G	p.Thr120Thr	synonymous	Exon 5 of 8	ENSP00000573287.1
	PELI1	ENST00000924986.1		c.291C>G	p.Thr97Thr	synonymous	Exon 4 of 7	ENSP00000595045.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1332530 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 669948

African (AFR) AF: 0.00 AC: 0 AN: 31970

American (AMR) AF: 0.00 AC: 0 AN: 44068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25344

East Asian (EAS) AF: 0.00 AC: 0 AN: 38428

South Asian (SAS) AF: 0.00 AC: 0 AN: 83262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5532

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 994646

Other (OTH) AF: 0.00 AC: 0 AN: 55962

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.7
DANN	Benign	0.67
PhyloP100		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs329498; hg19: chr2-64327544;