10-10462995-C-T

Position:

• chr10-10462995-C-T

Variant summary

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

The NM_001326319.2(CELF2):​c.-133+409C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,830 control chromosomes in the GnomAD database, including 26,462 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 0.59 (26462 hom., cov: 31)
• Consequence: CELF2 NM_001326319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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]

ENSG00000289328 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326319.2	c.-133+409C>T		intron_variant			NP_001313248.1
CELF2	NM_001326323.2	c.-189+409C>T		intron_variant			NP_001313252.1
CELF2	NM_001326321.2	c.-95+409C>T		intron_variant			NP_001313250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000289328	ENST00000684874.1	n.523C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89405 AN: 151712 Hom.: 26434 Cov.: 31

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.589 AC: 89478 AN: 151830 Hom.: 26462 Cov.: 31 AF XY: 0.592 AC XY: 43872 AN XY: 74168

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.589

Alfa AF: 0.361 Hom.: 658

Bravo AF: 0.595

Asia WGS AF: 0.594 AC: 2066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2243539; hg19: chr10-10504958;