rs3781053

Positions:

• chr10-11317506-G-A

Variant summary

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

The ENST00000633077.2(CELF2):​c.1096+3248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,140 control chromosomes in the GnomAD database, including 7,520 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 0.31 (7520 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CELF2 ENST00000633077.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420

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]

CELF2-AS1 (HGNC:23515): (CELF2 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.1096+3248G>A		intron_variant		ENST00000633077.2	NP_001313271.1
CELF2-AS1	NR_126062.1	n.1900C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.1096+3248G>A		intron_variant		1	NM_001326342.2	ENSP00000488690	P1
CELF2-AS1	ENST00000379256.4	n.1796C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46881 AN: 152022 Hom.: 7520 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.332

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.308 AC: 46895 AN: 152140 Hom.: 7520 Cov.: 33 AF XY: 0.305 AC XY: 22693 AN XY: 74352

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.330

Alfa AF: 0.302 Hom.: 9308

Bravo AF: 0.324

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.4
DANN	Benign	0.72

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: rs3781053; hg19: chr10-11359469;