10-10951863-A-G

Variant names:

• chr10-10951863-A-G
• rs201071
• ENST00000428520.7:n.275+75T>C

Variant summary

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

The ENST00000428520.7(LINC00710):​n.275+75T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,438 control chromosomes in the GnomAD database, including 4,068 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 0.17 (4065 hom., cov: 32)
  • Exomes 𝑓: 0.084 (3 hom.)
• Consequence: LINC00710 ENST00000428520.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	NM_001326325.2		c.146+31864A>G		intron	N/A	NP_001313254.1
	CELF2	NM_001326327.2		c.89+31864A>G		intron	N/A	NP_001313256.1
	CELF2	NM_001326326.2		c.89+31864A>G		intron	N/A	NP_001313255.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00710	ENST00000428520.7	TSL:1	n.275+75T>C		intron	N/A
	LINC00710	ENST00000635670.2	TSL:1	n.224+75T>C		intron	N/A
	LINC00710	ENST00000450174.2	TSL:5	n.233T>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26427 AN: 152082 Hom.: 4047 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.0293

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0746

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.0840 AC: 20 AN: 238 Hom.: 3 Cov.: 0 AF XY: 0.0722 AC XY: 13 AN XY: 180

African (AFR) AF: 0.667 AC: 4 AN: 6

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.125 AC: 1 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0619 AC: 13 AN: 210

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.174 AC: 26504 AN: 152200 Hom.: 4065 Cov.: 32 AF XY: 0.171 AC XY: 12695 AN XY: 74444

African (AFR) AF: 0.392 AC: 16278 AN: 41496

American (AMR) AF: 0.242 AC: 3692 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3470

East Asian (EAS) AF: 0.0293 AC: 152 AN: 5180

South Asian (SAS) AF: 0.0404 AC: 195 AN: 4826

European-Finnish (FIN) AF: 0.0347 AC: 368 AN: 10612

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0745 AC: 5067 AN: 68018

Other (OTH) AF: 0.166 AC: 350 AN: 2110

Alfa AF: 0.0961 Hom.: 1852

Bravo AF: 0.199

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs201071; hg19: chr10-10993826;