18-37323896-A-G

Variant names:

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

Variant summary

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

The NM_020180.4(CELF4):​c.370-2015T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,050 control chromosomes in the GnomAD database, including 21,972 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 0.53 (21972 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 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.370-2015T>C		intron	N/A	NP_064565.1
	CELF4	NM_001353740.2		c.370-2015T>C		intron	N/A	NP_001340669.1
	CELF4	NM_001353749.2		c.370-2015T>C		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>C		intron	N/A	ENSP00000410584.2
	CELF4	ENST00000591282.5	TSL:1	c.370-2015T>C		intron	N/A	ENSP00000464794.1
	CELF4	ENST00000603232.6	TSL:1	c.370-2015T>C		intron	N/A	ENSP00000474788.2

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80702 AN: 151932 Hom.: 21958 Cov.: 33

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.531 AC: 80764 AN: 152050 Hom.: 21972 Cov.: 33 AF XY: 0.538 AC XY: 40004 AN XY: 74316

African (AFR) AF: 0.609 AC: 25275 AN: 41470

American (AMR) AF: 0.567 AC: 8653 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1541 AN: 3468

East Asian (EAS) AF: 0.756 AC: 3908 AN: 5166

South Asian (SAS) AF: 0.730 AC: 3509 AN: 4810

European-Finnish (FIN) AF: 0.496 AC: 5248 AN: 10572

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30874 AN: 67974

Other (OTH) AF: 0.514 AC: 1088 AN: 2116

Alfa AF: 0.517 Hom.: 3600

Bravo AF: 0.531

Asia WGS AF: 0.734 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.59
PhyloP100		-0.097
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: rs2852373; hg19: chr18-34903859;