rs2067198042

Variant names:

• chr18-37253912-T-C
• rs2067198042
• NM_020180.4:c.1360A>G
• CELF4 p.Ser454Gly

Your query was ambiguous. Multiple possible variants found:

• chr18-37253912-T-C
• chr18-37253912-T-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020180.4(CELF4):​c.1360A>G​(p.Ser454Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,441,364 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CELF4 NM_020180.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.87
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020180.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF4	NM_020180.4	MANE Select	c.1360A>G	p.Ser454Gly	missense	Exon 12 of 13	NP_064565.1	Q9BZC1-1
	CELF4	NM_001353740.2		c.1439A>G	p.Gln480Arg	missense	Exon 13 of 15	NP_001340669.1
	CELF4	NM_001353749.2		c.1436A>G	p.Gln479Arg	missense	Exon 13 of 15	NP_001340678.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF4	ENST00000420428.7	TSL:5 MANE Select	c.1360A>G	p.Ser454Gly	missense	Exon 12 of 13	ENSP00000410584.2	Q9BZC1-1
	CELF4	ENST00000591282.5	TSL:1	c.1360A>G	p.Ser454Gly	missense	Exon 12 of 12	ENSP00000464794.1	Q9BZC1-1
	CELF4	ENST00000603232.6	TSL:1	c.1357A>G	p.Ser453Gly	missense	Exon 12 of 13	ENSP00000474788.2	Q9BZC1-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441364 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717574

African (AFR) AF: 0.00 AC: 0 AN: 32174

American (AMR) AF: 0.0000227 AC: 1 AN: 43958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25280

East Asian (EAS) AF: 0.00 AC: 0 AN: 37928

South Asian (SAS) AF: 0.00 AC: 0 AN: 85086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4990

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100678

Other (OTH) AF: 0.00 AC: 0 AN: 59080

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.77	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.019	D
Varity_R		0.67
gMVP		0.73
Mutation Taster		=56/44	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2067198042; hg19: chr18-34833875;