4-15033173-A-T

Variant names:

• chr4-15033173-A-T
• rs1247531935
• NM_001177382.2:c.2138A>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.2138A>T​(p.Tyr713Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. Y713S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPEB2 NM_001177382.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.40
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19173756).

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.2138A>T	p.Tyr713Phe	missense	Exon 5 of 12	NP_001170853.1	Q7Z5Q1-9
	CPEB2	NM_182485.3		c.2138A>T	p.Tyr713Phe	missense	Exon 5 of 11	NP_872291.2	A0A5K1VW93
	CPEB2	NM_001177381.2		c.2057A>T	p.Tyr686Phe	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.2138A>T	p.Tyr713Phe	missense	Exon 5 of 12	ENSP00000443985.1	Q7Z5Q1-9
	CPEB2	ENST00000507071.6	TSL:1	c.2138A>T	p.Tyr713Phe	missense	Exon 5 of 11	ENSP00000424084.2	A0A5K1VW93
	CPEB2	ENST00000382395.8	TSL:1	c.2048A>T	p.Tyr683Phe	missense	Exon 4 of 11	ENSP00000371832.4	A0A5K1VW71

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000540 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Benign	0.89
DEOGEN2	Benign	0.0076	T
Eigen	Benign	0.076
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.30	N
PhyloP100		6.4
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.21
Sift	Benign	0.30	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.45
MutPred		0.28		Gain of sheet (P = 0.0061)
MVP		0.49
MPC		0.31
ClinPred		0.80	D
GERP RS		5.5
Varity_R		0.32
gMVP		0.35
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: rs1247531935; hg19: chr4-15034797;