NM_020180.4:c.370-3267G>A

Variant names:

• chr18-37325148-C-T
• rs608489
• NM_020180.4:c.370-3267G>A

Variant summary

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

The NM_020180.4(CELF4):​c.370-3267G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,666 control chromosomes in the GnomAD database, including 18,804 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 0.49 (18804 hom., cov: 31)
• Consequence: CELF4 NM_020180.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.50
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF4	NM_020180.4	c.370-3267G>A		intron_variant	Intron 2 of 12	ENST00000420428.7	NP_064565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF4	ENST00000420428.7	c.370-3267G>A		intron_variant	Intron 2 of 12	5	NM_020180.4	ENSP00000410584.2
CELF4	ENST00000603232.6	c.370-3267G>A		intron_variant	Intron 2 of 12	1		ENSP00000474788.2
CELF4	ENST00000361795.9	c.370-3267G>A		intron_variant	Intron 2 of 12	2		ENSP00000355089.4

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74901 AN: 151550 Hom.: 18799 Cov.: 31

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.494 AC: 74935 AN: 151666 Hom.: 18804 Cov.: 31 AF XY: 0.503 AC XY: 37249 AN XY: 74118

African (AFR) AF: 0.481 AC: 19885 AN: 41366

American (AMR) AF: 0.554 AC: 8453 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1555 AN: 3468

East Asian (EAS) AF: 0.750 AC: 3779 AN: 5038

South Asian (SAS) AF: 0.727 AC: 3487 AN: 4796

European-Finnish (FIN) AF: 0.497 AC: 5250 AN: 10554

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30824 AN: 67892

Other (OTH) AF: 0.493 AC: 1036 AN: 2100

Alfa AF: 0.481 Hom.: 10248

Bravo AF: 0.489

Asia WGS AF: 0.722 AC: 2510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.48
PhyloP100		-4.5
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: rs608489; hg19: chr18-34905111;