chr4-15002876-C-T

Variant names:

• chr4-15002876-C-T
• rs920277251
• NM_001177382.2:c.203C>T

Variant summary

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

The NM_001177382.2(CPEB2):​c.203C>T​(p.Pro68Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,519,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: CPEB2 NM_001177382.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.735
• Publications: 0 publications found

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

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=0.19101143).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177382.2. 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
	CPEB2	NM_001177382.2	MANE Select	c.203C>T	p.Pro68Leu	missense	Exon 1 of 12	NP_001170853.1	Q7Z5Q1-9
	CPEB2	NM_182485.3		c.203C>T	p.Pro68Leu	missense	Exon 1 of 11	NP_872291.2	A0A5K1VW93
	CPEB2	NM_001177381.2		c.203C>T	p.Pro68Leu	missense	Exon 1 of 11	NP_001170852.1	Q7Z5Q1-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB2	ENST00000538197.7	TSL:5 MANE Select	c.203C>T	p.Pro68Leu	missense	Exon 1 of 12	ENSP00000443985.1	Q7Z5Q1-9
	CPEB2	ENST00000507071.6	TSL:1	c.203C>T	p.Pro68Leu	missense	Exon 1 of 11	ENSP00000424084.2	A0A5K1VW93
	CPEB2	ENST00000382395.8	TSL:1	c.203C>T	p.Pro68Leu	missense	Exon 1 of 11	ENSP00000371832.4	A0A5K1VW71

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151478 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: 0.0000442

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000853 AC: 1 AN: 117180 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.0000211

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000154 AC: 21 AN: 1367706 Hom.: 0 Cov.: 32 AF XY: 0.0000148 AC XY: 10 AN XY: 674790

African (AFR) AF: 0.00 AC: 0 AN: 30244

American (AMR) AF: 0.00 AC: 0 AN: 30316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24372

East Asian (EAS) AF: 0.00 AC: 0 AN: 35646

South Asian (SAS) AF: 0.00 AC: 0 AN: 76710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5158

European-Non Finnish (NFE) AF: 0.0000186 AC: 20 AN: 1074618

Other (OTH) AF: 0.0000175 AC: 1 AN: 57116

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151478 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 73940

African (AFR) AF: 0.00 AC: 0 AN: 41256

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5010

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67826

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000189

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	0.17
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.098	N
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.84	T
PhyloP100		0.73
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.052
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.030	D
Vest4		0.17
MutPred		0.30		Gain of sheet (P = 0.0043)
MVP		0.19
MPC		0.32
ClinPred		0.83	D
GERP RS		2.5
PromoterAI		-0.0074	Neutral
gMVP		0.079
Mutation Taster		=96/4	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: rs920277251; hg19: chr4-15004500;