Variant 18-37270883-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_020180.4(CELF4):c.984C>T(p.Ala328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,612,020 control chromosomes in the GnomAD database, including 91,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.29 ( 6822 hom., cov: 33)

Exomes 𝑓: 0.33 ( 84606 hom. )

Consequence

CELF4
NM_020180.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.476

Variant links:

Genes affected

CELF4 (HGNC:14015): (CUGBP Elav-like family member 4) 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CELF4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 18-37270883-G-A is Benign according to our data. Variant chr18-37270883-G-A is described in ClinVar as [Benign]. Clinvar id is 3060581.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.476 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF4	NM_020180.4 linkuse as main transcript	c.984C>T	p.Ala328=	synonymous_variant	8/13	ENST00000420428.7	NP_064565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF4	ENST00000420428.7 linkuse as main transcript	c.984C>T	p.Ala328=	synonymous_variant	8/13	5	NM_020180.4	ENSP00000410584	P4	Q9BZC1-1

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43549

AN:

152052

Hom.:

6822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.288

AC:

71441

AN:

248060

Hom.:

11236

AF XY:

0.292

AC XY:

39219

AN XY:

134162

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.410

Gnomad EAS exome

AF:

0.242

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.334

AC:

487559

AN:

1459850

Hom.:

84606

Cov.:

AF XY:

0.332

AC XY:

240746

AN XY:

726156

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.413

Gnomad4 EAS exome

AF:

0.251

Gnomad4 SAS exome

AF:

0.216

Gnomad4 FIN exome

AF:

0.325

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.327

GnomAD4 genome

AF:

0.286

AC:

43543

AN:

152170

Hom.:

6822

Cov.:

AF XY:

0.282

AC XY:

20957

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.178

Gnomad4 AMR

AF:

0.233

Gnomad4 ASJ

AF:

0.412

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.359

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.309

Hom.:

2129

Bravo

AF:

0.274

Asia WGS

AF:

0.256

AC:

894

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CELF4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

5.6

DANN

Benign

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over