4-15002870-C-T

Variant names:

• chr4-15002870-C-T
• rs1354457675
• NM_001177382.2:c.197C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001177382.2(CPEB2):​c.197C>T​(p.Ser66Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict 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. S66Y) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: CPEB2 NM_001177382.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

Genes affected

CPEB2 (HGNC:21745): (cytoplasmic polyadenylation element binding protein 2) The protein encoded by this gene is highly similar to cytoplasmic polyadenylation element binding protein (CPEB), an mRNA-binding protein that regulates cytoplasmic polyadenylation of mRNA as a trans factor in oogenesis and spermatogenesis. Studies of the similar gene in mice suggested a possible role of this protein in transcriptionally inactive haploid spermatids. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15429384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB2	NM_001177382.2	c.197C>T	p.Ser66Phe	missense_variant	Exon 1 of 12	ENST00000538197.7	NP_001170853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB2	ENST00000538197.7	c.197C>T	p.Ser66Phe	missense_variant	Exon 1 of 12	5	NM_001177382.2	ENSP00000443985.1

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151534 Hom.: 0 Cov.: 31

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151534 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 73990

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.11	N
M_CAP	Pathogenic	0.62	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.67	N;N
REVEL	Benign	0.092
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0040	D;D
Vest4		0.10
MutPred		0.21		Loss of glycosylation at S66 (P = 0.0168);Loss of glycosylation at S66 (P = 0.0168);
MVP		0.14
MPC		0.35
ClinPred		0.42	T
GERP RS		2.5
gMVP		0.047

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

Publications

LitVar

Other links and lift over

dbSNP: rs1354457675; hg19: chr4-15004494;