rs1247924

Variant names:

• chr18-37320056-A-G
• rs649456
• NM_020180.4:c.448+1747T>C

Your query was ambiguous. Multiple possible variants found:

• chr18-37320056-A-G
• chr18-37320056-A-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.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
• Publications: 2 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=-1.01).
• 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 rank	MANE	Protein	UniProt
CELF4	NM_020180.4	c.448+1747T>C		intron_variant	Intron 3 of 12	ENST00000420428.7	NP_064565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF4	ENST00000420428.7	c.448+1747T>C		intron_variant	Intron 3 of 12	5	NM_020180.4	ENSP00000410584.2
CELF4	ENST00000603232.6	c.448+1747T>C		intron_variant	Intron 3 of 12	1		ENSP00000474788.2
CELF4	ENST00000361795.9	c.448+1747T>C		intron_variant	Intron 3 of 12	2		ENSP00000355089.4

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

African (AFR) AF: 0.591 AC: 24451 AN: 41388

American (AMR) AF: 0.562 AC: 8580 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1501 AN: 3464

East Asian (EAS) AF: 0.755 AC: 3887 AN: 5146

South Asian (SAS) AF: 0.741 AC: 3567 AN: 4816

European-Finnish (FIN) AF: 0.477 AC: 5034 AN: 10554

Middle Eastern (MID) AF: 0.510 AC: 146 AN: 286

European-Non Finnish (NFE) AF: 0.440 AC: 29841 AN: 67782

Other (OTH) AF: 0.503 AC: 1059 AN: 2104

Alfa AF: 0.474 Hom.: 2159

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
PhyloP100		-1.4
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: rs649456; hg19: chr18-34900019;