NM_020180.4:c.287-11458C>T

Variant names:

• chr18-37497065-G-A
• rs1786814
• NM_020180.4:c.287-11458C>T

Variant summary

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

The NM_020180.4(CELF4):​c.287-11458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,156 control chromosomes in the GnomAD database, including 2,134 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 0.15 (2134 hom., cov: 32)
• Consequence: CELF4 NM_020180.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 39 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF4	NM_020180.4	c.287-11458C>T		intron_variant	Intron 1 of 12	ENST00000420428.7	NP_064565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF4	ENST00000420428.7	c.287-11458C>T		intron_variant	Intron 1 of 12	5	NM_020180.4	ENSP00000410584.2
CELF4	ENST00000603232.6	c.287-11458C>T		intron_variant	Intron 1 of 12	1		ENSP00000474788.2
CELF4	ENST00000361795.9	c.287-11458C>T		intron_variant	Intron 1 of 12	2		ENSP00000355089.4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23223 AN: 152038 Hom.: 2135 Cov.: 32

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.153 AC: 23224 AN: 152156 Hom.: 2134 Cov.: 32 AF XY: 0.156 AC XY: 11586 AN XY: 74372

African (AFR) AF: 0.0682 AC: 2830 AN: 41526

American (AMR) AF: 0.131 AC: 1997 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3470

East Asian (EAS) AF: 0.0645 AC: 334 AN: 5176

South Asian (SAS) AF: 0.250 AC: 1201 AN: 4800

European-Finnish (FIN) AF: 0.232 AC: 2455 AN: 10578

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13191 AN: 67982

Other (OTH) AF: 0.166 AC: 352 AN: 2116

Alfa AF: 0.170 Hom.: 4584

Bravo AF: 0.137

Asia WGS AF: 0.146 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.1
DANN	Benign	0.33
PhyloP100		0.23
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: rs1786814; hg19: chr18-35077028;