10-10958376-G-T

Position:

• chr10-10958376-G-T

Variant summary

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

The NM_001326325.2(CELF2):​c.146+38377G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,998 control chromosomes in the GnomAD database, including 12,175 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 0.32 (12175 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.146+38377G>T		intron_variant			NP_001313254.1
CELF2	NM_001326327.2	c.89+38377G>T		intron_variant			NP_001313256.1
CELF2	NM_001326326.2	c.89+38377G>T		intron_variant			NP_001313255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000637215.1	c.89+38377G>T		intron_variant		5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.89+38377G>T		intron_variant		5		ENSP00000489955.1
CELF2	ENST00000638035.1	c.-20+38377G>T		intron_variant		5		ENSP00000490401.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48925 AN: 151880 Hom.: 12137 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0959

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.322 AC: 49007 AN: 151998 Hom.: 12175 Cov.: 32 AF XY: 0.311 AC XY: 23094 AN XY: 74306

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.0959

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0954

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.289

Alfa AF: 0.200 Hom.: 7373

Bravo AF: 0.350

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.44
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62209; hg19: chr10-11000339;