rs10838725

Variant names:

• chr11-47536319-T-C
• rs10838725
• NM_001376376.1:c.-154+16673A>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.-154+16673A>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 152,088 control chromosomes in the GnomAD database, including 5,027 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 (5027 hom., cov: 32)
• Consequence: CELF1 NM_001376376.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 123 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376376.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF1	NM_001376376.1	MANE Select	c.-154+16673A>G		intron	N/A	NP_001363305.1	G5EA30
	CELF1	NM_001376370.1		c.-82+16673A>G		intron	N/A	NP_001363299.1	G5EA30
	CELF1	NM_001376371.1		c.-154+301A>G		intron	N/A	NP_001363300.1	G5EA30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF1	ENST00000687097.1	MANE Select	c.-154+16673A>G		intron	N/A	ENSP00000508525.1	G5EA30
	CELF1	ENST00000310513.10	TSL:1	c.-11+16673A>G		intron	N/A	ENSP00000308386.5	Q92879-2
	CELF1	ENST00000531165.5	TSL:2	c.-154+16673A>G		intron	N/A	ENSP00000436864.1	G5EA30

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34617 AN: 151968 Hom.: 5030 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.228 AC: 34606 AN: 152088 Hom.: 5027 Cov.: 32 AF XY: 0.227 AC XY: 16904 AN XY: 74318

African (AFR) AF: 0.0565 AC: 2348 AN: 41536

American (AMR) AF: 0.223 AC: 3403 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1174 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1815 AN: 5170

South Asian (SAS) AF: 0.456 AC: 2199 AN: 4818

European-Finnish (FIN) AF: 0.218 AC: 2306 AN: 10564

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

European-Non Finnish (NFE) AF: 0.302 AC: 20526 AN: 67970

Other (OTH) AF: 0.276 AC: 580 AN: 2100

Alfa AF: 0.265 Hom.: 7977

Bravo AF: 0.216

Asia WGS AF: 0.393 AC: 1368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.35
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10838725; hg19: chr11-47557871;