NM_021938.4:c.395-539C>T

Variant names:

• chr19-3275317-C-T
• rs312926
• NM_021938.4:c.395-539C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021938.4(CELF5):​c.395-539C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,080 control chromosomes in the GnomAD database, including 19,084 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 0.49 (19084 hom., cov: 32)
• Consequence: CELF5 NM_021938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 4 publications found

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]

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 (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021938.4. 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
	CELF5	NM_021938.4	MANE Select	c.395-539C>T		intron	N/A	NP_068757.2
	CELF5	NM_001172673.2		c.395-539C>T		intron	N/A	NP_001166144.1
	CELF5	NR_033342.2		n.477-539C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF5	ENST00000292672.7	TSL:1 MANE Select	c.395-539C>T		intron	N/A	ENSP00000292672.1
	CELF5	ENST00000541430.6	TSL:1	c.395-539C>T		intron	N/A	ENSP00000443498.1
	CELF5	ENST00000588350.1	TSL:1	n.-23-539C>T		intron	N/A	ENSP00000468503.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73866 AN: 151962 Hom.: 19066 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.486 AC: 73952 AN: 152080 Hom.: 19084 Cov.: 32 AF XY: 0.481 AC XY: 35728 AN XY: 74316

African (AFR) AF: 0.674 AC: 27981 AN: 41498

American (AMR) AF: 0.414 AC: 6327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1434 AN: 3466

East Asian (EAS) AF: 0.258 AC: 1330 AN: 5156

South Asian (SAS) AF: 0.414 AC: 1998 AN: 4826

European-Finnish (FIN) AF: 0.434 AC: 4580 AN: 10564

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29074 AN: 67962

Other (OTH) AF: 0.437 AC: 924 AN: 2114

Alfa AF: 0.442 Hom.: 15707

Bravo AF: 0.492

Asia WGS AF: 0.406 AC: 1412 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	1.8
DANN	Benign	0.57
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs312926; hg19: chr19-3275315;