chr4-15033164-G-A

Variant names:

• chr4-15033164-G-A
• rs769116648
• NM_001177382.2:c.2129G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001177382.2(CPEB2):​c.2129G>A​(p.Arg710Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000483 in 1,449,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CPEB2 NM_001177382.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.86
• 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]

C1QTNF7-AS1 (HGNC:40683): (C1QTNF7 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28775376).

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.2129G>A	p.Arg710Gln	missense	Exon 5 of 12	NP_001170853.1	Q7Z5Q1-9
	CPEB2	NM_182485.3		c.2129G>A	p.Arg710Gln	missense	Exon 5 of 11	NP_872291.2	A0A5K1VW93
	CPEB2	NM_001177381.2		c.2048G>A	p.Arg683Gln	missense	Exon 4 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.2129G>A	p.Arg710Gln	missense	Exon 5 of 12	ENSP00000443985.1	Q7Z5Q1-9
	CPEB2	ENST00000507071.6	TSL:1	c.2129G>A	p.Arg710Gln	missense	Exon 5 of 11	ENSP00000424084.2	A0A5K1VW93
	CPEB2	ENST00000382395.8	TSL:1	c.2039G>A	p.Arg680Gln	missense	Exon 4 of 11	ENSP00000371832.4	A0A5K1VW71

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000283 AC: 7 AN: 247676 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.00000483 AC: 7 AN: 1449960 Hom.: 0 Cov.: 27 AF XY: 0.00000277 AC XY: 2 AN XY: 721908

African (AFR) AF: 0.00 AC: 0 AN: 33014

American (AMR) AF: 0.0000908 AC: 4 AN: 44030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103390

Other (OTH) AF: 0.0000167 AC: 1 AN: 60008

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

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	0.21
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.22
Sift	Uncertain	0.019	D
Sift4G	Benign	0.063	T
Polyphen		0.86	P
Vest4		0.42
MutPred		0.33		Loss of methylation at R273 (P = 0.0136)
MVP		0.65
MPC		0.44
ClinPred		0.56	D
GERP RS		5.5
Varity_R		0.34
gMVP		0.73
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs769116648; hg19: chr4-15034788;