18-37323896-A-T

Variant names:

• chr18-37323896-A-T
• rs2852373
• NM_020180.4:c.370-2015T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020180.4(CELF4):​c.370-2015T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CELF4 NM_020180.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.370-2015T>A		intron	N/A	NP_064565.1
	CELF4	NM_001353740.2		c.370-2015T>A		intron	N/A	NP_001340669.1
	CELF4	NM_001353749.2		c.370-2015T>A		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.370-2015T>A		intron	N/A	ENSP00000410584.2
	CELF4	ENST00000591282.5	TSL:1	c.370-2015T>A		intron	N/A	ENSP00000464794.1
	CELF4	ENST00000603232.6	TSL:1	c.370-2015T>A		intron	N/A	ENSP00000474788.2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.75
PhyloP100		-0.097

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: rs2852373; hg19: chr18-34903859;