18-37269279-T-C

Variant names:

• chr18-37269279-T-C
• rs1662910
• NM_020180.4:c.1099+1489A>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.1099+1489A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,926 control chromosomes in the GnomAD database, including 18,351 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 0.48 (18351 hom., cov: 31)
• Consequence: CELF4 NM_020180.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF4	NM_020180.4	c.1099+1489A>G		intron_variant	Intron 8 of 12	ENST00000420428.7	NP_064565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF4	ENST00000420428.7	c.1099+1489A>G		intron_variant	Intron 8 of 12	5	NM_020180.4	ENSP00000410584.2
CELF4	ENST00000603232.6	c.1096+1489A>G		intron_variant	Intron 8 of 12	1		ENSP00000474788.2
CELF4	ENST00000361795.9	c.1093+1489A>G		intron_variant	Intron 8 of 12	2		ENSP00000355089.4

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73603 AN: 151808 Hom.: 18330 Cov.: 31

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.485 AC: 73664 AN: 151926 Hom.: 18351 Cov.: 31 AF XY: 0.480 AC XY: 35633 AN XY: 74258

African (AFR) AF: 0.556 AC: 23023 AN: 41410

American (AMR) AF: 0.418 AC: 6387 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1933 AN: 3466

East Asian (EAS) AF: 0.245 AC: 1263 AN: 5162

South Asian (SAS) AF: 0.276 AC: 1327 AN: 4810

European-Finnish (FIN) AF: 0.494 AC: 5215 AN: 10566

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32864 AN: 67930

Other (OTH) AF: 0.483 AC: 1021 AN: 2112

Alfa AF: 0.483 Hom.: 54768

Bravo AF: 0.483

Asia WGS AF: 0.325 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.55
PhyloP100		-0.18
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: rs1662910; hg19: chr18-34849242;