chr11-47472254-C-T

Variant names:

• chr11-47472254-C-T
• rs145495807
• NM_001376376.1:c.1521G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001376376.1(CELF1):​c.1521G>A​(p.Ser507Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,614,156 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (6 hom.)
• Consequence: CELF1 NM_001376376.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0270
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-47472254-C-T is Benign according to our data. Variant chr11-47472254-C-T is described in ClinVar as Benign. ClinVar VariationId is 791545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.027 with no splicing effect.
• BS2: High AC in GnomAd4 at 295 AD gene.

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.1521G>A	p.Ser507Ser	synonymous	Exon 15 of 15	NP_001363305.1	G5EA30
	CELF1	NM_001330272.2		c.1521G>A	p.Ser507Ser	synonymous	Exon 15 of 16	NP_001317201.1	G5EA30
	CELF1	NM_001376369.1		c.1521G>A	p.Ser507Ser	synonymous	Exon 15 of 15	NP_001363298.1	G5EA30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF1	ENST00000687097.1	MANE Select	c.1521G>A	p.Ser507Ser	synonymous	Exon 15 of 15	ENSP00000508525.1	G5EA30
	CELF1	ENST00000532048.5	TSL:1	c.1515G>A	p.Ser505Ser	synonymous	Exon 15 of 16	ENSP00000435926.1	Q92879-4
	CELF1	ENST00000358597.7	TSL:1	c.1437G>A	p.Ser479Ser	synonymous	Exon 12 of 13	ENSP00000351409.3	Q92879-1

Frequencies

GnomAD3 genomes AF: 0.00194 AC: 295 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00242 AC: 608 AN: 251388 AF XY: 0.00259

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00115

Gnomad NFE exome AF: 0.00293

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00213 AC: 3115 AN: 1461832 Hom.: 6 Cov.: 30 AF XY: 0.00219 AC XY: 1596 AN XY: 727218

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.000805 AC: 36 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 263 AN: 26136

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.00292 AC: 252 AN: 86256

European-Finnish (FIN) AF: 0.00103 AC: 55 AN: 53420

Middle Eastern (MID) AF: 0.00940 AC: 54 AN: 5744

European-Non Finnish (NFE) AF: 0.00207 AC: 2300 AN: 1111978

Other (OTH) AF: 0.00224 AC: 135 AN: 60394

GnomAD4 genome AF: 0.00194 AC: 295 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.00196 AC XY: 146 AN XY: 74486

African (AFR) AF: 0.000337 AC: 14 AN: 41584

American (AMR) AF: 0.00131 AC: 20 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4820

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00276 AC: 188 AN: 68020

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00325 Hom.: 0

Bravo AF: 0.00175

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.00344

EpiControl AF: 0.00344

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		-0.027
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs145495807; hg19: chr11-47493806;