Variant chr18-37270882-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020180.4(CELF4):c.985G>A(p.Val329Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,936 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CELF4
NM_020180.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF4	NM_020180.4 linkuse as main transcript	c.985G>A	p.Val329Met	missense_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.985G>A	p.Val329Met	missense_variant	8/13	5	NM_020180.4	ENSP00000410584	P4	Q9BZC1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249412

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460936

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.985G>A (p.V329M) alteration is located in exon 8 (coding exon 8) of the CELF4 gene. This alteration results from a G to A substitution at nucleotide position 985, causing the valine (V) at amino acid position 329 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;.;.;T;.;.;.;T;.;.;.;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Benign

0.0039

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D;D;.;D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.56

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.8

.;.;.;L;.;.;.;L;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.6

.;N;.;.;.;.;.;.;.;.;.;.

REVEL

Uncertain

0.32

Sift

Benign

0.33

.;T;.;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.26

T;T;T;T;T;T;T;T;T;.;T;.

Polyphen

0.99, 0.95, 0.92, 0.86, 0.99

.;D;P;P;.;P;.;P;.;.;D;.

Vest4

0.70, 0.73, 0.75, 0.74, 0.72, 0.76, 0.75, 0.72

MutPred

0.30

.;.;.;Gain of glycosylation at P330 (P = 0.1012);.;.;.;Gain of glycosylation at P330 (P = 0.1012);.;.;.;.;

MVP

0.67

MPC

0.98

ClinPred

0.96

GERP RS

4.7

Varity_R

0.23

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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