Menu
GeneBe

18-37273128-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_020180.4(CELF4):c.837C>T(p.Val279=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000812 in 1,613,236 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00084 ( 3 hom. )

Consequence

CELF4
NM_020180.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.804
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-37273128-G-A is Benign according to our data. Variant chr18-37273128-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3049299.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.804 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 80 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CELF4NM_020180.4 linkuse as main transcriptc.837C>T p.Val279= synonymous_variant 7/13 ENST00000420428.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CELF4ENST00000420428.7 linkuse as main transcriptc.837C>T p.Val279= synonymous_variant 7/135 NM_020180.4 P4Q9BZC1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000526
AC:
80
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000926
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000463
AC:
116
AN:
250444
Hom.:
0
AF XY:
0.000450
AC XY:
61
AN XY:
135572
show subpopulations
Gnomad AFR exome
AF:
0.0000619
Gnomad AMR exome
AF:
0.000521
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000788
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000842
AC:
1230
AN:
1461008
Hom.:
3
Cov.:
30
AF XY:
0.000797
AC XY:
579
AN XY:
726728
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000425
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.0000377
Gnomad4 NFE exome
AF:
0.00105
Gnomad4 OTH exome
AF:
0.000447
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000526
AC:
80
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.000444
AC XY:
33
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.000338
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000926
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000564
Hom.:
0
Bravo
AF:
0.000608
EpiCase
AF:
0.000927
EpiControl
AF:
0.000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

CELF4-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 19, 2019This variant is classified as likely 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
-0.36
Cadd
Benign
7.8
Dann
Benign
0.66

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

LitVar

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

Other links and lift over

dbSNP: rs142389555; hg19: chr18-34853091; COSMIC: COSV58450630; COSMIC: COSV58450630; API