11-47552529-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001376376.1(CELF1):c.-154+463G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,322 control chromosomes in the GnomAD database, including 37 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 0.020 (37 hom., cov: 32)
• Consequence: CELF1 NM_001376376.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809

Genes affected

CELF1 (HGNC:2549): (CUGBP Elav-like family member 1) 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. This gene may play a role in myotonic dystrophy type 1 (DM1) via interactions with the dystrophia myotonica-protein kinase (DMPK) gene. 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=-0.83).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0196 (2991/152322) while in subpopulation AFR AF= 0.0291 (1209/41566). AF 95% confidence interval is 0.0277. There are 37 homozygotes in gnomad4. There are 1397 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 2988 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF1	NM_001376376.1	c.-154+463G>C		intron_variant		ENST00000687097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF1	ENST00000687097.1	c.-154+463G>C		intron_variant			NM_001376376.1	P3

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2988 AN: 152204 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0230

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

GnomAD4 genome AF: 0.0196 AC: 2991 AN: 152322 Hom.: 37 Cov.: 32 AF XY: 0.0188 AC XY: 1397 AN XY: 74492

Gnomad4 AFR AF: 0.0291

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00592 Hom.: 1

Bravo AF: 0.0218

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	14
Dann	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60206633; hg19: chr11-47574081;