11-47508472-G-A

Variant names:

• chr11-47508472-G-A
• rs6485758
• NM_001376376.1:c.-153-7540C>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.-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
• Publications: 13 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 = 0.44 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF1	NM_001376376.1	MANE Select	c.-153-7540C>T		intron	N/A	NP_001363305.1
	CELF1	NM_001330272.2		c.-153-7540C>T		intron	N/A	NP_001317201.1
	CELF1	NM_001376369.1		c.-153-7540C>T		intron	N/A	NP_001363298.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF1	ENST00000687097.1	MANE Select	c.-153-7540C>T		intron	N/A	ENSP00000508525.1
	CELF1	ENST00000532048.5	TSL:1	c.-153-7540C>T		intron	N/A	ENSP00000435926.1
	CELF1	ENST00000310513.10	TSL:1	c.-10-19448C>T		intron	N/A	ENSP00000308386.5

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

African (AFR) AF: 0.0568 AC: 2334 AN: 41094

American (AMR) AF: 0.224 AC: 3382 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1168 AN: 3458

East Asian (EAS) AF: 0.354 AC: 1816 AN: 5132

South Asian (SAS) AF: 0.456 AC: 2171 AN: 4756

European-Finnish (FIN) AF: 0.220 AC: 2249 AN: 10226

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.302 AC: 20487 AN: 67734

Other (OTH) AF: 0.276 AC: 578 AN: 2096

Alfa AF: 0.171 Hom.: 465

Bravo AF: 0.216

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.5
DANN	Benign	0.56
PhyloP100		0.77
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: rs6485758; hg19: chr11-47530024;