rs7933019

Variant names:

• chr11-47487585-G-C
• rs7933019
• NM_001376376.1:c.260-344C>G

Variant summary

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

The NM_001376376.1(CELF1):​c.260-344C>G 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 152,108 control chromosomes in the GnomAD database, including 5,043 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 (5043 hom., cov: 32)
• Consequence: CELF1 NM_001376376.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 14 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF1	NM_001376376.1	c.260-344C>G		intron_variant	Intron 4 of 14	ENST00000687097.1	NP_001363305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF1	ENST00000687097.1	c.260-344C>G		intron_variant	Intron 4 of 14		NM_001376376.1	ENSP00000508525.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34669 AN: 151988 Hom.: 5046 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.228 AC: 34657 AN: 152108 Hom.: 5043 Cov.: 32 AF XY: 0.228 AC XY: 16933 AN XY: 74342

African (AFR) AF: 0.0564 AC: 2342 AN: 41524

American (AMR) AF: 0.223 AC: 3411 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1176 AN: 3472

East Asian (EAS) AF: 0.352 AC: 1818 AN: 5162

South Asian (SAS) AF: 0.457 AC: 2200 AN: 4812

European-Finnish (FIN) AF: 0.218 AC: 2303 AN: 10580

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20561 AN: 67962

Other (OTH) AF: 0.277 AC: 586 AN: 2114

Alfa AF: 0.258 Hom.: 707

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	3.0
DANN	Benign	0.63
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7933019; hg19: chr11-47509137;