NM_020180.4:c.1084A>G

Variant names:

• chr18-37270783-T-C
• rs372922900
• NM_020180.4:c.1084A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_020180.4(CELF4):​c.1084A>G​(p.Ile362Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: CELF4 NM_020180.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36095303).
• BS2: High AC in GnomAdExome4 at 41 AD gene.

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.1084A>G	p.Ile362Val	missense	Exon 8 of 13	NP_064565.1	Q9BZC1-1
	CELF4	NM_001353740.2		c.1084A>G	p.Ile362Val	missense	Exon 8 of 15	NP_001340669.1
	CELF4	NM_001353749.2		c.1081A>G	p.Ile361Val	missense	Exon 8 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.1084A>G	p.Ile362Val	missense	Exon 8 of 13	ENSP00000410584.2	Q9BZC1-1
	CELF4	ENST00000591282.5	TSL:1	c.1084A>G	p.Ile362Val	missense	Exon 8 of 12	ENSP00000464794.1	Q9BZC1-1
	CELF4	ENST00000603232.6	TSL:1	c.1081A>G	p.Ile361Val	missense	Exon 8 of 13	ENSP00000474788.2	Q9BZC1-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000281 AC: 41 AN: 1461646 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111944

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

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	Benign	0.20
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	T
Eigen	Benign	0.022
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.7
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.23
Sift	Benign	0.44	T
Sift4G	Benign	0.56	T
Polyphen		0.19	B
Vest4		0.61
MVP		0.55
MPC		0.31
ClinPred		0.82	D
GERP RS		4.7
PromoterAI		0.075	Neutral
Varity_R		0.14
gMVP		0.25
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs372922900; hg19: chr18-34850746;