Genetic Variant NCL:p.Glu149Glu (chr2-231461706-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005381.3(NCL):c.447G>A(p.Glu149Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,562 control chromosomes in the GnomAD database, including 49,426 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 0.29 ( 7875 hom., cov: 33)

Exomes 𝑓: 0.22 ( 41551 hom. )

Consequence

NCL
NM_005381.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.38

Publications

28 publications found

Variant links:

Genes affected

NCL (HGNC:7667): (nucleolin) Nucleolin (NCL), a eukaryotic nucleolar phosphoprotein, is involved in the synthesis and maturation of ribosomes. It is located mainly in dense fibrillar regions of the nucleolus. Human NCL gene consists of 14 exons with 13 introns and spans approximately 11kb. The intron 11 of the NCL gene encodes a small nucleolar RNA, termed U20. [provided by RefSeq, Jul 2008]

NCL links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-6.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCL	NM_005381.3 link	c.447G>A	p.Glu149Glu	synonymous_variant	Exon 3 of 14	ENST00000322723.9	NP_005372.2	P19338B3KM80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCL	ENST00000322723.9 link	c.447G>A	p.Glu149Glu	synonymous_variant	Exon 3 of 14	2	NM_005381.3	ENSP00000318195.4		P19338

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44682

AN:

151976

Hom.:

7860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.454

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.289

GnomAD2 exomes

AF:

0.287

AC:

71963

AN:

250796

AF XY:

0.282

show subpopulations

Gnomad AFR exome

AF:

0.460

Gnomad AMR exome

AF:

0.337

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.583

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.216

AC:

315850

AN:

1461468

Hom.:

41551

Cov.:

AF XY:

0.221

AC XY:

160369

AN XY:

727068

show subpopulations

African (AFR)

AF:

0.457

AC:

15291

AN:

33466

American (AMR)

AF:

0.332

AC:

14850

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

5445

AN:

26134

East Asian (EAS)

AF:

0.605

AC:

24012

AN:

39694

South Asian (SAS)

AF:

0.385

AC:

33229

AN:

86244

European-Finnish (FIN)

AF:

0.256

AC:

13679

AN:

53418

Middle Eastern (MID)

AF:

0.221

AC:

1274

AN:

5766

European-Non Finnish (NFE)

AF:

0.174

AC:

193256

AN:

1111666

Other (OTH)

AF:

0.245

AC:

14814

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

14557

29114

43670

58227

72784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7194

14388

21582

28776

35970

<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:

0.294

AC:

44732

AN:

152094

Hom.:

7875

Cov.:

AF XY:

0.298

AC XY:

22181

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.454

AC:

18816

AN:

41482

American (AMR)

AF:

0.288

AC:

4400

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

698

AN:

3466

East Asian (EAS)

AF:

0.581

AC:

2992

AN:

5154

South Asian (SAS)

AF:

0.408

AC:

1968

AN:

4820

European-Finnish (FIN)

AF:

0.250

AC:

2647

AN:

10588

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.181

AC:

12319

AN:

67982

Other (OTH)

AF:

0.294

AC:

622

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1533

3065

4598

6130

7663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.226

Hom.:

16125

Bravo

AF:

0.303

Asia WGS

AF:

0.516

AC:

1789

AN:

3478

EpiCase

AF:

0.191

EpiControl

AF:

0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.031

(source)

DANN

Benign

0.76

PhyloP100

-6.4

Mutation Taster

=100/0

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