chr11-47550727-G-A

Variant names:

• chr11-47550727-G-A
• rs11039290
• NM_001376376.1:c.-154+2265C>T

Variant summary

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

The NM_001376376.1(CELF1):​c.-154+2265C>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 151,564 control chromosomes in the GnomAD database, including 4,993 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 (4993 hom., cov: 31)
• Consequence: CELF1 NM_001376376.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• 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 rank	MANE	Protein	UniProt
CELF1	NM_001376376.1	c.-154+2265C>T		intron_variant	Intron 1 of 14	ENST00000687097.1	NP_001363305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF1	ENST00000687097.1	c.-154+2265C>T		intron_variant	Intron 1 of 14		NM_001376376.1	ENSP00000508525.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34521 AN: 151446 Hom.: 4996 Cov.: 31

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.228

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: 34509 AN: 151564 Hom.: 4993 Cov.: 31 AF XY: 0.227 AC XY: 16838 AN XY: 74020

African (AFR) AF: 0.0572 AC: 2366 AN: 41370

American (AMR) AF: 0.223 AC: 3400 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1174 AN: 3470

East Asian (EAS) AF: 0.350 AC: 1803 AN: 5158

South Asian (SAS) AF: 0.456 AC: 2195 AN: 4810

European-Finnish (FIN) AF: 0.219 AC: 2274 AN: 10394

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20465 AN: 67840

Other (OTH) AF: 0.275 AC: 577 AN: 2096

Alfa AF: 0.102 Hom.: 189

Bravo AF: 0.216

Asia WGS AF: 0.391 AC: 1360 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.54
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11039290; hg19: chr11-47572279;