Genetic Variant CELF2:c.976+61C>T (chr10-11288613-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001326342.2(CELF2):c.976+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,588,636 control chromosomes in the GnomAD database, including 68,272 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 0.33 ( 8986 hom., cov: 32)

Exomes 𝑓: 0.28 ( 59286 hom. )

Consequence

CELF2
NM_001326342.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.884

Publications

5 publications found

Variant links:

Genes affected

CELF2 (HGNC:2550): (CUGBP Elav-like family member 2) Members of the CELF/BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing, and translation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

CELF2 links:

CELF2-AS1 (HGNC:23515): (CELF2 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

CELF2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326342.2 link	c.976+61C>T		intron_variant	Intron 9 of 12	ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2 link	c.976+61C>T		intron_variant	Intron 9 of 12	1	NM_001326342.2	ENSP00000488690.1		E9PC62

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

50002

AN:

151886

Hom.:

8984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.444

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.548

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.310

GnomAD4 exome

AF:

0.281

AC:

403420

AN:

1436632

Hom.:

59286

AF XY:

0.283

AC XY:

201902

AN XY:

713310

show subpopulations

African (AFR)

AF:

0.452

AC:

14932

AN:

33008

American (AMR)

AF:

0.351

AC:

14771

AN:

42120

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

5872

AN:

25328

East Asian (EAS)

AF:

0.512

AC:

19826

AN:

38760

South Asian (SAS)

AF:

0.378

AC:

31736

AN:

84024

European-Finnish (FIN)

AF:

0.243

AC:

11787

AN:

48436

Middle Eastern (MID)

AF:

0.282

AC:

1609

AN:

5710

European-Non Finnish (NFE)

AF:

0.260

AC:

285704

AN:

1099762

Other (OTH)

AF:

0.289

AC:

17183

AN:

59484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

14786

29572

44357

59143

73929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10016

20032

30048

40064

50080

<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:

0.329

AC:

50037

AN:

152004

Hom.:

8986

Cov.:

AF XY:

0.330

AC XY:

24547

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.444

AC:

18370

AN:

41418

American (AMR)

AF:

0.329

AC:

5030

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

785

AN:

3468

East Asian (EAS)

AF:

0.547

AC:

2828

AN:

5166

South Asian (SAS)

AF:

0.372

AC:

1797

AN:

4826

European-Finnish (FIN)

AF:

0.253

AC:

2672

AN:

10568

Middle Eastern (MID)

AF:

0.271

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.259

AC:

17612

AN:

67968

Other (OTH)

AF:

0.308

AC:

649

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1693

3386

5080

6773

8466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.276

Hom.:

6469

Bravo

AF:

0.339

Asia WGS

AF:

0.421

AC:

1461

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

(source)

DANN

Benign

0.82

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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