11-47478715-T-C

Position:

• chr11-47478715-T-C

Variant summary

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

The NM_001376376.1(CELF1):​c.844+162A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,080 control chromosomes in the GnomAD database, including 10,462 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 0.35 (10462 hom., cov: 32)
• Consequence: CELF1 NM_001376376.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF1	NM_001376376.1	c.844+162A>G		intron_variant		ENST00000687097.1	NP_001363305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF1	ENST00000687097.1	c.844+162A>G		intron_variant			NM_001376376.1	ENSP00000508525	P3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53135 AN: 151962 Hom.: 10463 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.349 AC: 53132 AN: 152080 Hom.: 10462 Cov.: 32 AF XY: 0.346 AC XY: 25722 AN XY: 74322

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.394

Alfa AF: 0.430 Hom.: 19412

Bravo AF: 0.336

Asia WGS AF: 0.457 AC: 1589 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	0.20
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242081; hg19: chr11-47500267;