NM_020180.4:c.287-38097T>G

Variant names:

• chr18-37523704-A-C
• rs4799934
• NM_020180.4:c.287-38097T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020180.4(CELF4):​c.287-38097T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,258 control chromosomes in the GnomAD database, including 60,792 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 0.89 (60792 hom., cov: 34)
• Consequence: CELF4 NM_020180.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020180.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF4	NM_020180.4	MANE Select	c.287-38097T>G		intron	N/A	NP_064565.1
	CELF4	NM_001353740.2		c.287-38097T>G		intron	N/A	NP_001340669.1
	CELF4	NM_001353749.2		c.287-38097T>G		intron	N/A	NP_001340678.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF4	ENST00000420428.7	TSL:5 MANE Select	c.287-38097T>G		intron	N/A	ENSP00000410584.2
	CELF4	ENST00000591282.5	TSL:1	c.287-38097T>G		intron	N/A	ENSP00000464794.1
	CELF4	ENST00000603232.6	TSL:1	c.287-38097T>G		intron	N/A	ENSP00000474788.2

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135461 AN: 152140 Hom.: 60757 Cov.: 34

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.915

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.890 AC: 135547 AN: 152258 Hom.: 60792 Cov.: 34 AF XY: 0.892 AC XY: 66388 AN XY: 74458

African (AFR) AF: 0.804 AC: 33372 AN: 41526

American (AMR) AF: 0.797 AC: 12193 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3370 AN: 3470

East Asian (EAS) AF: 0.966 AC: 4995 AN: 5172

South Asian (SAS) AF: 0.897 AC: 4328 AN: 4824

European-Finnish (FIN) AF: 0.956 AC: 10152 AN: 10614

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64134 AN: 68036

Other (OTH) AF: 0.913 AC: 1931 AN: 2114

Alfa AF: 0.914 Hom.: 77121

Bravo AF: 0.871

Asia WGS AF: 0.911 AC: 3168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.46
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4799934; hg19: chr18-35103667;