19-3251221-T-G

Variant names:

• chr19-3251221-T-G
• rs17764205
• NM_021938.4:c.342+154T>G

Variant summary

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

The NM_021938.4(CELF5):​c.342+154T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,984 control chromosomes in the GnomAD database, including 3,551 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 0.20 (3551 hom., cov: 31)
• Consequence: CELF5 NM_021938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF5	NM_021938.4	c.342+154T>G		intron_variant	Intron 2 of 12	ENST00000292672.7	NP_068757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF5	ENST00000292672.7	c.342+154T>G		intron_variant	Intron 2 of 12	1	NM_021938.4	ENSP00000292672.1
CELF5	ENST00000541430.6	c.342+154T>G		intron_variant	Intron 2 of 11	1		ENSP00000443498.1
CELF5	ENST00000334293.10	n.-1+154T>G		intron_variant	Intron 2 of 12	2		ENSP00000335182.6

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30588 AN: 151866 Hom.: 3535 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.202 AC: 30645 AN: 151984 Hom.: 3551 Cov.: 31 AF XY: 0.210 AC XY: 15624 AN XY: 74312

African (AFR) AF: 0.233 AC: 9648 AN: 41476

American (AMR) AF: 0.220 AC: 3357 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3468

East Asian (EAS) AF: 0.546 AC: 2797 AN: 5124

South Asian (SAS) AF: 0.321 AC: 1547 AN: 4812

European-Finnish (FIN) AF: 0.213 AC: 2252 AN: 10568

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10073 AN: 67970

Other (OTH) AF: 0.196 AC: 412 AN: 2104

Alfa AF: 0.166 Hom.: 3890

Bravo AF: 0.203

Asia WGS AF: 0.426 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.58
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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: rs17764205; hg19: chr19-3251219; COSMIC: COSV53014280;