19-3293595-A-G

Position:

• chr19-3293595-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172673.2(CELF5):​c.*261A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 947,640 control chromosomes in the GnomAD database, including 251,455 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 0.74 (41752 hom., cov: 27)
  • Exomes 𝑓: 0.72 (209703 hom.)
• Consequence: CELF5 NM_001172673.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.05

Genes affected

CELF5 (HGNC:14058): (CUGBP Elav-like family member 5) This gene encodes a member of the the CELF/BRUNOL protein family, which 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. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

CELF5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF5	NM_021938.4	c.*40+109A>G		intron_variant		ENST00000292672.7	NP_068757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF5	ENST00000541430.6	c.*261A>G		3_prime_UTR_variant	12/12	1		ENSP00000443498.1
CELF5	ENST00000292672.7	c.*40+109A>G		intron_variant		1	NM_021938.4	ENSP00000292672.1
CELF5	ENST00000588350.1	n.*152+109A>G		intron_variant		1		ENSP00000468503.1
CELF5	ENST00000334293.10	n.*152+109A>G		intron_variant		2		ENSP00000335182.6

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111107 AN: 151082 Hom.: 41700 Cov.: 27

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.717 AC: 571111 AN: 796442 Hom.: 209703 Cov.: 10 AF XY: 0.714 AC XY: 286604 AN XY: 401476

Gnomad4 AFR exome AF: 0.812

Gnomad4 AMR exome AF: 0.662

Gnomad4 ASJ exome AF: 0.781

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.695

Gnomad4 NFE exome AF: 0.752

Gnomad4 OTH exome AF: 0.722

GnomAD4 genome AF: 0.736 AC: 111215 AN: 151198 Hom.: 41752 Cov.: 27 AF XY: 0.726 AC XY: 53596 AN XY: 73822

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.754

Alfa AF: 0.739 Hom.: 85623

Bravo AF: 0.738

Asia WGS AF: 0.483 AC: 1685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.028
DANN	Benign	0.30

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: rs313784; hg19: chr19-3293593;