rs731229

Variant names:

• chr10-10926670-C-T
• rs731229
• ENST00000661059.1:n.1966G>A

Variant summary

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

The ENST00000661059.1(LINC00710):​n.1966G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,978 control chromosomes in the GnomAD database, including 7,451 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 0.30 (7451 hom., cov: 31)
• Consequence: LINC00710 ENST00000661059.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.146+6671C>T		intron_variant	Intron 3 of 15		NP_001313254.1
CELF2	NM_001326327.2	c.89+6671C>T		intron_variant	Intron 2 of 14		NP_001313256.1
CELF2	NM_001326326.2	c.89+6671C>T		intron_variant	Intron 2 of 14		NP_001313255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC00710	ENST00000661059.1	n.1966G>A		non_coding_transcript_exon_variant	Exon 7 of 7
LINC00710	ENST00000668056.1	n.1246G>A		non_coding_transcript_exon_variant	Exon 7 of 7
LINC00710	ENST00000670911.1	n.1182G>A		non_coding_transcript_exon_variant	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44872 AN: 151860 Hom.: 7437 Cov.: 31

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.296 AC: 44920 AN: 151978 Hom.: 7451 Cov.: 31 AF XY: 0.304 AC XY: 22558 AN XY: 74292

African (AFR) AF: 0.286 AC: 11864 AN: 41430

American (AMR) AF: 0.423 AC: 6466 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 890 AN: 3464

East Asian (EAS) AF: 0.705 AC: 3624 AN: 5142

South Asian (SAS) AF: 0.348 AC: 1679 AN: 4818

European-Finnish (FIN) AF: 0.289 AC: 3051 AN: 10550

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16471 AN: 67988

Other (OTH) AF: 0.299 AC: 630 AN: 2108

Alfa AF: 0.265 Hom.: 19211

Bravo AF: 0.310

Asia WGS AF: 0.515 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.79
PhyloP100		-0.094

Splicing

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

Other links and lift over

dbSNP: rs731229; hg19: chr10-10968633;