rs3780993

Positions:

• chr10-11273150-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001326342.2(CELF2):​c.778-1907G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 152,104 control chromosomes in the GnomAD database, including 635 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 0.081 (635 hom., cov: 31)
• Consequence: CELF2 NM_001326342.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

Genes affected

CELF2 (HGNC:2550): (CUGBP Elav-like family member 2) 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. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF2	NM_001326342.2	c.778-1907G>A		intron_variant		ENST00000633077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF2	ENST00000633077.2	c.778-1907G>A		intron_variant		1	NM_001326342.2	P1

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12300 AN: 151986 Hom.: 634 Cov.: 31

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.0981

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.0809 AC: 12309 AN: 152104 Hom.: 635 Cov.: 31 AF XY: 0.0810 AC XY: 6021 AN XY: 74352

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0654

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.0981

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.103 Hom.: 1180

Bravo AF: 0.0811

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.94
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs3780993; hg19: chr10-11315113;