1-151709048-C-A

Variant names:

• chr1-151709048-C-A
• rs202171109
• NM_007185.7:c.436G>T

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>T​(p.Ala146Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A146T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CELF3 NM_007185.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 0 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=0.19532904).

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>T	p.Ala146Ser	missense	Exon 5 of 13	NP_009116.3
	CELF3	NM_001291106.2		c.436G>T	p.Ala146Ser	missense	Exon 5 of 13	NP_001278035.1	Q5SZQ8-2
	CELF3	NM_001291107.2		c.433G>T	p.Ala145Ser	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>T	p.Ala146Ser	missense	Exon 5 of 13	ENSP00000290583.4	Q5SZQ8-1
	CELF3	ENST00000290585.8	TSL:1	c.436G>T	p.Ala146Ser	missense	Exon 5 of 12	ENSP00000290585.4	Q5SZQ8-4
	CELF3	ENST00000420342.1	TSL:5	c.436G>T	p.Ala146Ser	missense	Exon 6 of 14	ENSP00000402503.1	H0Y623

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461734 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727156

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.00 AC: 0 AN: 39696

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111936

Other (OTH) AF: 0.00 AC: 0 AN: 60386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.025	N
PhyloP100		2.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.47	N
REVEL	Uncertain	0.30
Sift	Benign	0.28	T
Sift4G	Benign	0.71	T
Polyphen		0.0020	B
Vest4		0.42
MutPred		0.27		Gain of disorder (P = 0.056)
MVP		0.84
MPC		1.3
ClinPred		0.74	D
GERP RS		4.4
Varity_R		0.070
gMVP		0.69
Mutation Taster		=64/36	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;