4-15003032-A-G

Variant names:

• chr4-15003032-A-G
• rs1473027270
• NM_001177382.2:c.359A>G

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.359A>G​(p.Asp120Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000222 in 1,349,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D120V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CPEB2 NM_001177382.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.228
• 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=0.08644155).

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.359A>G	p.Asp120Gly	missense	Exon 1 of 12	NP_001170853.1	Q7Z5Q1-9
	CPEB2	NM_182485.3		c.359A>G	p.Asp120Gly	missense	Exon 1 of 11	NP_872291.2	A0A5K1VW93
	CPEB2	NM_001177381.2		c.359A>G	p.Asp120Gly	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.359A>G	p.Asp120Gly	missense	Exon 1 of 12	ENSP00000443985.1	Q7Z5Q1-9
	CPEB2	ENST00000507071.6	TSL:1	c.359A>G	p.Asp120Gly	missense	Exon 1 of 11	ENSP00000424084.2	A0A5K1VW93
	CPEB2	ENST00000382395.8	TSL:1	c.359A>G	p.Asp120Gly	missense	Exon 1 of 11	ENSP00000371832.4	A0A5K1VW71

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.0000103 AC: 1 AN: 97324 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: 0.0000255

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000222 AC: 3 AN: 1349140 Hom.: 0 Cov.: 41 AF XY: 0.00000150 AC XY: 1 AN XY: 665318

African (AFR) AF: 0.00 AC: 0 AN: 29240

American (AMR) AF: 0.00 AC: 0 AN: 25594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22786

East Asian (EAS) AF: 0.00 AC: 0 AN: 35228

South Asian (SAS) AF: 0.00 AC: 0 AN: 74124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 0.00000281 AC: 3 AN: 1067694

Other (OTH) AF: 0.00 AC: 0 AN: 56230

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.15
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	19
DANN	Benign	0.96
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.076	N
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.23
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.13
Sift	Uncertain	0.015	D
Sift4G	Benign	0.13	T
Vest4		0.023
MutPred		0.052		Loss of solvent accessibility (P = 0.1177)
MVP		0.18
MPC		0.42
ClinPred		0.18	T
GERP RS		-2.1
PromoterAI		0.093	Neutral
gMVP		0.021
Mutation Taster		=97/3	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: rs1473027270; hg19: chr4-15004656;