rs7604693

Positions:

• chr2-64122068-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000358912.5(PELI1):​c.-69-13689G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,004 control chromosomes in the GnomAD database, including 53,382 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 0.83 (53382 hom., cov: 30)
• Consequence: PELI1 ENST00000358912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PELI1	NM_020651.4	c.-69-13689G>T		intron_variant		ENST00000358912.5	NP_065702.2
PELI1	XM_011532994.4	c.-70+332G>T		intron_variant			XP_011531296.1
PELI1	XM_017004520.2	c.-69-13689G>T		intron_variant			XP_016860009.1
PELI1	XM_047445137.1	c.-179-9396G>T		intron_variant			XP_047301093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PELI1	ENST00000358912.5	c.-69-13689G>T		intron_variant		1	NM_020651.4	ENSP00000351789	P1
PELI1	ENST00000466177.6	n.283-13689G>T		intron_variant, non_coding_transcript_variant		5
PELI1	ENST00000468869.2	n.526-13689G>T		intron_variant, non_coding_transcript_variant		4
PELI1	ENST00000494203.1	n.341-13689G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126585 AN: 151886 Hom.: 53314 Cov.: 30

Gnomad AFR AF: 0.952

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.795

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.834 AC: 126716 AN: 152004 Hom.: 53382 Cov.: 30 AF XY: 0.835 AC XY: 62049 AN XY: 74336

Gnomad4 AFR AF: 0.952

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.799

Alfa AF: 0.776 Hom.: 50565

Bravo AF: 0.838

Asia WGS AF: 0.903 AC: 3134 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.49

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: rs7604693; hg19: chr2-64349202;