rs596406

Positions:

• chr10-11182702-T-C

Variant summary

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

The ENST00000633077.2(CELF2):​c.271+17020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,140 control chromosomes in the GnomAD database, including 2,466 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 0.14 (2466 hom., cov: 32)
• Consequence: CELF2 ENST00000633077.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.271+17020T>C		intron_variant		ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.271+17020T>C		intron_variant		1	NM_001326342.2	ENSP00000488690	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21501 AN: 152020 Hom.: 2457 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0358

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0840

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.142 AC: 21545 AN: 152140 Hom.: 2466 Cov.: 32 AF XY: 0.139 AC XY: 10308 AN XY: 74378

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0359

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0840

Gnomad4 NFE AF: 0.0797

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0867 Hom.: 1169

Bravo AF: 0.148

Asia WGS AF: 0.0930 AC: 326 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	2.3
DANN	Benign	0.51

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: rs596406; hg19: chr10-11224665;