10-10923586-A-G

Variant names:

• chr10-10923586-A-G
• rs2146551
• NM_001326325.2:c.146+3587A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001326325.2(CELF2):​c.146+3587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,134 control chromosomes in the GnomAD database, including 13,187 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 0.39 (13187 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 1 publications found

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]

LINC00710 (HGNC:27386): (long intergenic non-protein coding RNA 710)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.146+3587A>G		intron_variant	Intron 3 of 15		NP_001313254.1
CELF2	NM_001326327.2	c.89+3587A>G		intron_variant	Intron 2 of 14		NP_001313256.1
CELF2	NM_001326326.2	c.89+3587A>G		intron_variant	Intron 2 of 14		NP_001313255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000637215.1	c.89+3587A>G		intron_variant	Intron 2 of 14	5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.89+3587A>G		intron_variant	Intron 2 of 13	5		ENSP00000489955.1
CELF2	ENST00000638035.1	c.-20+3587A>G		intron_variant	Intron 3 of 14	5		ENSP00000490401.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59384 AN: 152016 Hom.: 13147 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.391 AC: 59483 AN: 152134 Hom.: 13187 Cov.: 32 AF XY: 0.397 AC XY: 29490 AN XY: 74374

African (AFR) AF: 0.550 AC: 22790 AN: 41466

American (AMR) AF: 0.477 AC: 7296 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 997 AN: 3472

East Asian (EAS) AF: 0.711 AC: 3681 AN: 5174

South Asian (SAS) AF: 0.362 AC: 1745 AN: 4820

European-Finnish (FIN) AF: 0.306 AC: 3234 AN: 10580

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18575 AN: 68010

Other (OTH) AF: 0.381 AC: 804 AN: 2112

Alfa AF: 0.305 Hom.: 12993

Bravo AF: 0.417

Asia WGS AF: 0.552 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Benign	0.52
PhyloP100		3.1

Splicing

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

Other links and lift over

dbSNP: rs2146551; hg19: chr10-10965549;