18-37365178-T-C

Variant names:

• chr18-37365178-T-C
• rs524513
• NM_020180.4:c.370-43297A>G

Variant summary

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

The NM_001353740.2(CELF4):​c.370-43297A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,144 control chromosomes in the GnomAD database, including 57,799 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 0.87 (57799 hom., cov: 31)
• Consequence: CELF4 NM_001353740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353740.2. 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.370-43297A>G		intron	N/A	NP_064565.1
	CELF4	NM_001353740.2		c.370-43297A>G		intron	N/A	NP_001340669.1
	CELF4	NM_001353749.2		c.370-43297A>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.370-43297A>G		intron	N/A	ENSP00000410584.2
	CELF4	ENST00000591282.5	TSL:1	c.370-43297A>G		intron	N/A	ENSP00000464794.1
	CELF4	ENST00000603232.6	TSL:1	c.370-43297A>G		intron	N/A	ENSP00000474788.2

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132070 AN: 152026 Hom.: 57732 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.869 AC: 132202 AN: 152144 Hom.: 57799 Cov.: 31 AF XY: 0.869 AC XY: 64645 AN XY: 74386

African (AFR) AF: 0.964 AC: 40007 AN: 41512

American (AMR) AF: 0.869 AC: 13297 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2620 AN: 3472

East Asian (EAS) AF: 0.922 AC: 4747 AN: 5148

South Asian (SAS) AF: 0.847 AC: 4090 AN: 4828

European-Finnish (FIN) AF: 0.818 AC: 8666 AN: 10590

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56125 AN: 67986

Other (OTH) AF: 0.839 AC: 1771 AN: 2112

Alfa AF: 0.858 Hom.: 7004

Bravo AF: 0.876

Asia WGS AF: 0.860 AC: 2989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.86
PhyloP100		-1.0
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: rs524513; hg19: chr18-34945141;