ENST00000428520.7:n.687+3500G>A

Variant names:

• chr10-10940683-C-T
• rs10795839
• ENST00000428520.7:n.687+3500G>A

Variant summary

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

The ENST00000428520.7(LINC00710):​n.687+3500G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,978 control chromosomes in the GnomAD database, including 10,042 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 0.35 (10042 hom., cov: 32)
• Consequence: LINC00710 ENST00000428520.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428520.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	NM_001326325.2		c.146+20684C>T		intron	N/A	NP_001313254.1
	CELF2	NM_001326327.2		c.89+20684C>T		intron	N/A	NP_001313256.1
	CELF2	NM_001326326.2		c.89+20684C>T		intron	N/A	NP_001313255.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00710	ENST00000428520.7	TSL:1	n.687+3500G>A		intron	N/A
	LINC00710	ENST00000635670.2	TSL:1	n.455+3500G>A		intron	N/A
	CELF2	ENST00000637215.1	TSL:5	c.89+20684C>T		intron	N/A	ENSP00000490185.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52577 AN: 151862 Hom.: 10030 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.346 AC: 52628 AN: 151978 Hom.: 10042 Cov.: 32 AF XY: 0.359 AC XY: 26681 AN XY: 74296

African (AFR) AF: 0.257 AC: 10663 AN: 41446

American (AMR) AF: 0.500 AC: 7630 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3468

East Asian (EAS) AF: 0.734 AC: 3788 AN: 5162

South Asian (SAS) AF: 0.499 AC: 2404 AN: 4816

European-Finnish (FIN) AF: 0.428 AC: 4514 AN: 10542

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.316 AC: 21508 AN: 67964

Other (OTH) AF: 0.375 AC: 793 AN: 2112

Alfa AF: 0.328 Hom.: 6270

Bravo AF: 0.347

Asia WGS AF: 0.591 AC: 2050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.42
DANN	Benign	0.20
PhyloP100		-0.57

Splicing

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

Other links and lift over

dbSNP: rs10795839; hg19: chr10-10982646;