rs779501534

Variant names:

• chr11-47484404-C-A
• rs779501534
• NM_001376376.1:c.511G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-47484404-C-A
• chr11-47484404-C-G
• chr11-47484404-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001376376.1(CELF1):​c.511G>T​(p.Asp171Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,642 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D171N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CELF1 NM_001376376.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.52

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF1	NM_001376376.1	c.511G>T	p.Asp171Tyr	missense_variant	Exon 7 of 15	ENST00000687097.1	NP_001363305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF1	ENST00000687097.1	c.511G>T	p.Asp171Tyr	missense_variant	Exon 7 of 15		NM_001376376.1	ENSP00000508525.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250230 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135332

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460642 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726630

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;.;T;.;.;.;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.99	D;D;D;.;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.;M;M;M;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.5	D;D;D;D;D;D;D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D
Polyphen		1.0	D;.;D;D;D;D;D
Vest4		0.66
MutPred		0.63		.;.;.;.;.;Gain of MoRF binding (P = 0.068);.;
MVP		0.87
MPC		1.2
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.94
gMVP		0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs779501534; hg19: chr11-47505956;