chr1-151709048-C-T

Variant names:

• chr1-151709048-C-T
• rs202171109
• NM_007185.7:c.436G>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.436G>A​(p.Ala146Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: CELF3 NM_007185.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43
• 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]

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=0.11422682).

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.436G>A	p.Ala146Thr	missense	Exon 5 of 13	NP_009116.3
	CELF3	NM_001291106.2		c.436G>A	p.Ala146Thr	missense	Exon 5 of 13	NP_001278035.1	Q5SZQ8-2
	CELF3	NM_001291107.2		c.433G>A	p.Ala145Thr	missense	Exon 5 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.436G>A	p.Ala146Thr	missense	Exon 5 of 13	ENSP00000290583.4	Q5SZQ8-1
	CELF3	ENST00000290585.8	TSL:1	c.436G>A	p.Ala146Thr	missense	Exon 5 of 12	ENSP00000290585.4	Q5SZQ8-4
	CELF3	ENST00000420342.1	TSL:5	c.436G>A	p.Ala146Thr	missense	Exon 6 of 14	ENSP00000402503.1	H0Y623

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151962 Hom.: 0 Cov.: 32

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: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000637 AC: 16 AN: 251178 AF XY: 0.0000516

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1461734 Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26 AN XY: 727156

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.000618 AC: 33 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111936

Other (OTH) AF: 0.0000662 AC: 4 AN: 60386

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151962 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74200

African (AFR) AF: 0.00 AC: 0 AN: 41348

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000906 AC: 11

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	0.070
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.80	N
PhyloP100		2.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.27
Sift	Benign	0.26	T
Sift4G	Benign	0.58	T
Polyphen		0.0080	B
Vest4		0.39
MutPred		0.26		Gain of catalytic residue at A146 (P = 0.1331)
MVP		0.89
MPC		1.3
ClinPred		0.078	T
GERP RS		4.4
Varity_R		0.062
gMVP		0.72
Mutation Taster		=55/45	polymorphism

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: rs202171109; hg19: chr1-151681524; COSMIC: COSV99310292; COSMIC: COSV99310292;