rs2067198042

Variant names:

• chr18-37253912-T-A
• NM_020180.4:c.1360A>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020180.4(CELF4):​c.1360A>T​(p.Ser454Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000416 in 1,441,364 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: CELF4 NM_020180.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF4	NM_020180.4	c.1360A>T	p.Ser454Cys	missense_variant	Exon 12 of 13	ENST00000420428.7	NP_064565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF4	ENST00000420428.7	c.1360A>T	p.Ser454Cys	missense_variant	Exon 12 of 13	5	NM_020180.4	ENSP00000410584.2
CELF4	ENST00000603232.6	c.1357A>T	p.Ser453Cys	missense_variant	Exon 12 of 13	1		ENSP00000474788.2
CELF4	ENST00000361795.9	c.1354A>T	p.Ser452Cys	missense_variant	Exon 12 of 13	2		ENSP00000355089.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000416 AC: 6 AN: 1441364 Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2 AN XY: 717574

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000545

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	.;.;.;T;.;.;.;T;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D;D;.;D;D
M_CAP	Pathogenic	0.80	D
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.0	.;.;.;M;.;.;.;M;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.8	.;D;.;.;.;.;.;.;.;.
REVEL	Benign	0.26
Sift	Uncertain	0.020	.;D;.;.;.;.;.;.;.;.
Sift4G	Uncertain	0.035	D;D;D;D;D;D;D;D;D;.
Polyphen		0.95, 0.95, 0.99, 0.99	.;P;P;D;.;D;.;D;.;.
Vest4		0.75, 0.75, 0.76, 0.75, 0.76, 0.71, 0.76
MutPred		0.46		.;.;.;Loss of disorder (P = 0.0137);.;.;.;Loss of disorder (P = 0.0137);.;.;
MVP		0.66
MPC		1.7
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.46
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-34833875;