rs201099

Positions:

• chr10-10982596-A-G

Variant summary

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

The NM_001326325.2(CELF2):​c.146+62597A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,136 control chromosomes in the GnomAD database, including 11,534 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 0.29 (11534 hom., cov: 31)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62

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 (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326317.2	c.-20+62597A>G		intron_variant			NP_001313246.1
CELF2	NM_001326318.2	c.-20+62597A>G		intron_variant			NP_001313247.1
CELF2	NM_001326319.2	c.-20+42142A>G		intron_variant			NP_001313248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000636488.1	c.89+62597A>G		intron_variant		5		ENSP00000489955
CELF2	ENST00000637215.1	c.89+62597A>G		intron_variant		5		ENSP00000490185
CELF2	ENST00000638035.1	c.-20+62597A>G		intron_variant		5		ENSP00000490401

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44587 AN: 152018 Hom.: 11498 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.0780

Gnomad FIN AF: 0.0566

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.294 AC: 44687 AN: 152136 Hom.: 11534 Cov.: 31 AF XY: 0.282 AC XY: 21004 AN XY: 74402

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0178

Gnomad4 SAS AF: 0.0781

Gnomad4 FIN AF: 0.0566

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.273

Alfa AF: 0.173 Hom.: 4357

Bravo AF: 0.327

Asia WGS AF: 0.116 AC: 404 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	0.092
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201099; hg19: chr10-11024559;