Genetic Variant NM_020651.4:c.291C>A (chr2-64100410-G-T) – 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.291C>A(p.Thr97Thr) 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
NM_020651.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.117

Publications

21 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=-0.41).

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 rank	MANE	Protein	UniProt
PELI1	NM_020651.4 link	c.291C>A	p.Thr97Thr	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.291C>A	p.Thr97Thr	synonymous_variant	Exon 4 of 7	1	NM_020651.4	ENSP00000351789.4		Q96FA3
PELI1	ENST00000466177.6 link	n.686C>A		non_coding_transcript_exon_variant	Exon 5 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41665

AN:

151494

Hom.:

6888

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.341

AC:

85319

AN:

249868

AF XY:

0.341

show subpopulations

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 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.:

AF XY:

0.297

AC XY:

196903

AN XY:

662582

show subpopulations

African (AFR)

AF:

0.109

AC:

3476

AN:

31852

American (AMR)

AF:

0.383

AC:

16805

AN:

43894

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

7430

AN:

25228

East Asian (EAS)

AF:

0.746

AC:

28586

AN:

38324

South Asian (SAS)

AF:

0.344

AC:

28523

AN:

82806

European-Finnish (FIN)

AF:

0.282

AC:

15036

AN:

53270

Middle Eastern (MID)

AF:

0.290

AC:

1598

AN:

5512

European-Non Finnish (NFE)

AF:

0.274

AC:

268913

AN:

980410

Other (OTH)

AF:

0.300

AC:

16637

AN:

55400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

Heterozygous variant carriers

11612

23224

34837

46449

58061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8446

16892

25338

33784

42230

<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:

0.275

AC:

41707

AN:

151610

Hom.:

6905

Cov.:

AF XY:

0.278

AC XY:

20574

AN XY:

74088

show subpopulations

African (AFR)

AF:

0.130

AC:

5380

AN:

41270

American (AMR)

AF:

0.331

AC:

5037

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1083

AN:

3464

East Asian (EAS)

AF:

0.738

AC:

3823

AN:

5182

South Asian (SAS)

AF:

0.377

AC:

1811

AN:

4806

European-Finnish (FIN)

AF:

0.282

AC:

2946

AN:

10458

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20630

AN:

67888

Other (OTH)

AF:

0.289

AC:

608

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1453

2906

4359

5812

7265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.263

Hom.:

3567

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

(source)

DANN

Benign

0.70

PhyloP100

-0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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