Genetic Variant NM_020651.4:c.243A>G (chr2-64100458-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_020651.4(PELI1):c.243A>G(p.Leu81Leu) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.117

Publications

18 publications found

Variant links:

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]

PELI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PELI1	NM_020651.4 link	c.243A>G	p.Leu81Leu	synonymous_variant	Exon 4 of 7	ENST00000358912.5	NP_065702.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PELI1	ENST00000358912.5 link	c.243A>G	p.Leu81Leu	synonymous_variant	Exon 4 of 7	1	NM_020651.4	ENSP00000351789.4		Q96FA3
PELI1	ENST00000466177.6 link	n.638A>G		non_coding_transcript_exon_variant	Exon 5 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40991

AN:

151928

Hom.:

6797

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.342

AC:

85781

AN:

251016

AF XY:

0.341

show subpopulations

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 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.:

AF XY:

0.310

AC XY:

218469

AN XY:

705120

show subpopulations

African (AFR)

AF:

0.0968

AC:

3206

AN:

33132

American (AMR)

AF:

0.385

AC:

17124

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

7722

AN:

25792

East Asian (EAS)

AF:

0.749

AC:

29333

AN:

39180

South Asian (SAS)

AF:

0.350

AC:

29759

AN:

85046

European-Finnish (FIN)

AF:

0.284

AC:

15134

AN:

53380

Middle Eastern (MID)

AF:

0.295

AC:

1679

AN:

5688

European-Non Finnish (NFE)

AF:

0.293

AC:

312489

AN:

1066410

Other (OTH)

AF:

0.311

AC:

18224

AN:

58558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

12988

25976

38965

51953

64941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10170

20340

30510

40680

50850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.270

AC:

41028

AN:

152046

Hom.:

6815

Cov.:

AF XY:

0.273

AC XY:

20259

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.114

AC:

4726

AN:

41506

American (AMR)

AF:

0.327

AC:

4994

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1084

AN:

3470

East Asian (EAS)

AF:

0.737

AC:

3814

AN:

5178

South Asian (SAS)

AF:

0.376

AC:

1808

AN:

4812

European-Finnish (FIN)

AF:

0.279

AC:

2944

AN:

10552

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20667

AN:

67950

Other (OTH)

AF:

0.286

AC:

604

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1405

2810

4215

5620

7025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.295

Hom.:

13352

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

(source)

DANN

Benign

0.80

PhyloP100

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over