ENST00000428520.7:n.687+1423T>C

Variant names:

• chr10-10942760-A-G
• rs1928724
• ENST00000428520.7:n.687+1423T>C

Variant summary

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

The ENST00000428520.7(LINC00710):​n.687+1423T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,016 control chromosomes in the GnomAD database, including 10,546 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 0.36 (10546 hom., cov: 32)
• Consequence: LINC00710 ENST00000428520.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 2 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 97

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.146+22761A>G		intron_variant	Intron 3 of 15		NP_001313254.1
CELF2	NM_001326327.2	c.89+22761A>G		intron_variant	Intron 2 of 14		NP_001313256.1
CELF2	NM_001326326.2	c.89+22761A>G		intron_variant	Intron 2 of 14		NP_001313255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC00710	ENST00000428520.7	n.687+1423T>C		intron_variant	Intron 5 of 5	1
LINC00710	ENST00000635670.2	n.455+1423T>C		intron_variant	Intron 3 of 4	1
CELF2	ENST00000637215.1	c.89+22761A>G		intron_variant	Intron 2 of 14	5		ENSP00000490185.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54405 AN: 151898 Hom.: 10540 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.358 AC: 54441 AN: 152016 Hom.: 10546 Cov.: 32 AF XY: 0.369 AC XY: 27458 AN XY: 74312

African (AFR) AF: 0.362 AC: 15009 AN: 41474

American (AMR) AF: 0.390 AC: 5952 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 970 AN: 3472

East Asian (EAS) AF: 0.802 AC: 4143 AN: 5166

South Asian (SAS) AF: 0.511 AC: 2456 AN: 4810

European-Finnish (FIN) AF: 0.445 AC: 4693 AN: 10542

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20147 AN: 67960

Other (OTH) AF: 0.361 AC: 761 AN: 2108

Alfa AF: 0.317 Hom.: 7961

Bravo AF: 0.358

Asia WGS AF: 0.604 AC: 2097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.63
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs1928724; hg19: chr10-10984723;