18-37320056-A-G

Position:

• chr18-37320056-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020180.4(CELF4):​c.448+1747T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,712 control chromosomes in the GnomAD database, including 20,822 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 0.52 (20822 hom., cov: 34)
• Consequence: CELF4 NM_020180.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF4	NM_020180.4	c.448+1747T>C		intron_variant		ENST00000420428.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF4	ENST00000420428.7	c.448+1747T>C		intron_variant		5	NM_020180.4	P4

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78524 AN: 151588 Hom.: 20807 Cov.: 34

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.518 AC: 78587 AN: 151712 Hom.: 20822 Cov.: 34 AF XY: 0.526 AC XY: 38997 AN XY: 74178

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.503

Alfa AF: 0.471 Hom.: 2044

Bravo AF: 0.518

Asia WGS AF: 0.734 AC: 2553 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	1.3
DANN	Benign	0.082

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

Publications

LitVar

Other links and lift over

dbSNP: rs649456; hg19: chr18-34900019;