rs6485758

Positions:

• chr11-47508472-G-A
• chr11-47508472-G-T

Variant summary

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

The NM_001376376.1(CELF1):​c.-153-7540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 150,808 control chromosomes in the GnomAD database, including 5,014 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 0.23 (5014 hom., cov: 28)
• Consequence: CELF1 NM_001376376.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF1	NM_001376376.1	c.-153-7540C>T		intron_variant		ENST00000687097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF1	ENST00000687097.1	c.-153-7540C>T		intron_variant			NM_001376376.1	P3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34454 AN: 150694 Hom.: 5017 Cov.: 28

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.228 AC: 34442 AN: 150808 Hom.: 5014 Cov.: 28 AF XY: 0.228 AC XY: 16803 AN XY: 73562

Gnomad4 AFR AF: 0.0568

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.276

Alfa AF: 0.176 Hom.: 463

Bravo AF: 0.216

Asia WGS AF: 0.393 AC: 1367 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	5.5
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6485758; hg19: chr11-47530024;