rs920277251

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-15002876-C-A
• chr4-15002876-C-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>A​(p.Pro68His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,367,706 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. 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. P68L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CPEB2 NM_001177382.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.20888013).

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>A	p.Pro68His	missense	Exon 1 of 12	NP_001170853.1	Q7Z5Q1-9
	CPEB2	NM_182485.3		c.203C>A	p.Pro68His	missense	Exon 1 of 11	NP_872291.2	A0A5K1VW93
	CPEB2	NM_001177381.2		c.203C>A	p.Pro68His	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>A	p.Pro68His	missense	Exon 1 of 12	ENSP00000443985.1	Q7Z5Q1-9
	CPEB2	ENST00000507071.6	TSL:1	c.203C>A	p.Pro68His	missense	Exon 1 of 11	ENSP00000424084.2	A0A5K1VW93
	CPEB2	ENST00000382395.8	TSL:1	c.203C>A	p.Pro68His	missense	Exon 1 of 11	ENSP00000371832.4	A0A5K1VW71

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1367706 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 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: 0.0000281 AC: 1 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: 9.31e-7 AC: 1 AN: 1074618

Other (OTH) AF: 0.00 AC: 0 AN: 57116

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.16	N
M_CAP	Pathogenic	0.73	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.73
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Vest4		0.16
MutPred		0.27		Gain of sheet (P = 0.0043)
MVP		0.17
MPC		0.37
ClinPred		0.46	T
GERP RS		2.5
PromoterAI		-0.22	Neutral
gMVP		0.10
Mutation Taster		=95/5	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;