rs773175289

Variant names:

• chr18-37270840-C-A
• rs773175289
• NM_020180.4:c.1027G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-37270840-C-A
• chr18-37270840-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020180.4(CELF4):​c.1027G>T​(p.Gly343Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G343S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CELF4 NM_020180.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF4	NM_020180.4	c.1027G>T	p.Gly343Cys	missense_variant	Exon 8 of 13	ENST00000420428.7	NP_064565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF4	ENST00000420428.7	c.1027G>T	p.Gly343Cys	missense_variant	Exon 8 of 13	5	NM_020180.4	ENSP00000410584.2
CELF4	ENST00000603232.6	c.1024G>T	p.Gly342Cys	missense_variant	Exon 8 of 13	1		ENSP00000474788.2
CELF4	ENST00000361795.9	c.1021G>T	p.Gly341Cys	missense_variant	Exon 8 of 13	2		ENSP00000355089.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	.;.;.;D;.;.;.;D;.;.;.;.
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;.;D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.76	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.098	D
MutationAssessor	Uncertain	2.4	.;.;.;M;.;.;.;M;.;.;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.3	.;D;.;.;.;.;.;.;.;.;.;.
REVEL	Uncertain	0.53
Sift	Uncertain	0.0070	.;D;.;.;.;.;.;.;.;.;.;.
Sift4G	Uncertain	0.016	D;D;D;T;T;T;D;T;D;.;D;.
Polyphen		1.0, 0.99, 0.99, 0.99	.;D;D;D;.;D;.;D;.;.;D;.
Vest4		0.86, 0.88, 0.87, 0.89, 0.89, 0.91, 0.87
MutPred		0.41		.;.;.;Loss of relative solvent accessibility (P = 0.0306);.;.;.;Loss of relative solvent accessibility (P = 0.0306);.;.;.;.;
MVP		0.86
MPC		1.1
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.24
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: -15

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs773175289; hg19: chr18-34850803;