1-151707576-C-T

Variant names:

• chr1-151707576-C-T
• rs764774518
• NM_007185.7:c.703G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007185.7(CELF3):​c.703G>A​(p.Val235Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,609,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: CELF3 NM_007185.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.50
• Publications: 1 publications found

Genes affected

CELF3 (HGNC:11967): (CUGBP Elav-like family member 3) 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. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2010]

ENSG00000227045 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21736321).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007185.7. 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
	CELF3	NM_007185.7	MANE Select	c.703G>A	p.Val235Met	missense	Exon 7 of 13	NP_009116.3
	CELF3	NM_001291106.2		c.703G>A	p.Val235Met	missense	Exon 7 of 13	NP_001278035.1	Q5SZQ8-2
	CELF3	NM_001291107.2		c.700G>A	p.Val234Met	missense	Exon 7 of 13	NP_001278036.1	Q5SZQ8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF3	ENST00000290583.9	TSL:1 MANE Select	c.703G>A	p.Val235Met	missense	Exon 7 of 13	ENSP00000290583.4	Q5SZQ8-1
	CELF3	ENST00000290585.8	TSL:1	c.703G>A	p.Val235Met	missense	Exon 7 of 12	ENSP00000290585.4	Q5SZQ8-4
	CELF3	ENST00000420342.1	TSL:5	c.703G>A	p.Val235Met	missense	Exon 8 of 14	ENSP00000402503.1	H0Y623

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000208 AC: 5 AN: 240890 AF XY: 0.0000381

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000558

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000199 AC: 29 AN: 1456928 Hom.: 0 Cov.: 32 AF XY: 0.0000207 AC XY: 15 AN XY: 724696

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39624

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111004

Other (OTH) AF: 0.0000332 AC: 2 AN: 60210

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152342 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74486

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.063
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.080
Sift	Benign	0.29	T
Sift4G	Benign	0.25	T
Polyphen		0.065	B
Vest4		0.44
MutPred		0.48		Gain of disorder (P = 0.0172)
MVP		0.20
MPC		0.37
ClinPred		0.34	T
GERP RS		4.0
Varity_R		0.11
gMVP		0.82
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs764774518; hg19: chr1-151680052;