18-37348676-C-T

Variant names:

• chr18-37348676-C-T
• rs4799915
• NM_020180.4:c.370-26795G>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.370-26795G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,866 control chromosomes in the GnomAD database, including 26,989 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 0.58 (26989 hom., cov: 31)
• Consequence: CELF4 NM_020180.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF4	NM_020180.4	c.370-26795G>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.370-26795G>A		intron_variant	Intron 2 of 12	5	NM_020180.4	ENSP00000410584.2
CELF4	ENST00000603232.6	c.370-26795G>A		intron_variant	Intron 2 of 12	1		ENSP00000474788.2
CELF4	ENST00000361795.9	c.370-26795G>A		intron_variant	Intron 2 of 12	2		ENSP00000355089.4

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87897 AN: 151748 Hom.: 26979 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.579 AC: 87927 AN: 151866 Hom.: 26989 Cov.: 31 AF XY: 0.584 AC XY: 43318 AN XY: 74204

African (AFR) AF: 0.355 AC: 14698 AN: 41378

American (AMR) AF: 0.665 AC: 10156 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1911 AN: 3468

East Asian (EAS) AF: 0.726 AC: 3732 AN: 5144

South Asian (SAS) AF: 0.644 AC: 3100 AN: 4810

European-Finnish (FIN) AF: 0.724 AC: 7646 AN: 10556

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44730 AN: 67932

Other (OTH) AF: 0.565 AC: 1191 AN: 2108

Alfa AF: 0.634 Hom.: 131039

Bravo AF: 0.563

Asia WGS AF: 0.642 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.49
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: rs4799915; hg19: chr18-34928639;