4-15007404-A-T

Variant names:

• chr4-15007404-A-T
• rs111964119
• NM_001177382.2:c.1762A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001177382.2(CPEB2):​c.1762A>T​(p.Thr588Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,614,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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. T588A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: CPEB2 NM_001177382.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008636147).

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.1762A>T	p.Thr588Ser	missense	Exon 2 of 12	NP_001170853.1	Q7Z5Q1-9
	CPEB2	NM_182485.3		c.1762A>T	p.Thr588Ser	missense	Exon 2 of 11	NP_872291.2	A0A5K1VW93
	CPEB2	NM_001177381.2		c.1762A>T	p.Thr588Ser	missense	Exon 2 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.1762A>T	p.Thr588Ser	missense	Exon 2 of 12	ENSP00000443985.1	Q7Z5Q1-9
	CPEB2	ENST00000507071.6	TSL:1	c.1762A>T	p.Thr588Ser	missense	Exon 2 of 11	ENSP00000424084.2	A0A5K1VW93
	CPEB2	ENST00000382395.8	TSL:1	c.1762A>T	p.Thr588Ser	missense	Exon 2 of 11	ENSP00000371832.4	A0A5K1VW71

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 240 AN: 152216 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000505 AC: 127 AN: 251384 AF XY: 0.000316

Gnomad AFR exome AF: 0.00628

Gnomad AMR exome AF: 0.000608

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000173 AC: 253 AN: 1461768 Hom.: 1 Cov.: 31 AF XY: 0.000165 AC XY: 120 AN XY: 727190

African (AFR) AF: 0.00574 AC: 192 AN: 33474

American (AMR) AF: 0.000626 AC: 28 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111936

Other (OTH) AF: 0.000364 AC: 22 AN: 60392

GnomAD4 genome AF: 0.00156 AC: 237 AN: 152334 Hom.: 0 Cov.: 33 AF XY: 0.00148 AC XY: 110 AN XY: 74496

African (AFR) AF: 0.00546 AC: 227 AN: 41584

American (AMR) AF: 0.000327 AC: 5 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.0000894 Hom.: 0

Bravo AF: 0.00159

ESP6500AA AF: 0.00613 AC: 27

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000560 AC: 68

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0030	T
Eigen	Benign	0.062
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.90	D
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.20	N
PhyloP100		3.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.091
Sift	Benign	0.46	T
Sift4G	Benign	0.84	T
Polyphen		0.0020	B
Vest4		0.26
MutPred		0.13		Loss of catalytic residue at T151 (P = 0.0385)
MVP		0.57
MPC		0.30
ClinPred		0.051	T
GERP RS		5.3
Varity_R		0.11
gMVP		0.17
Mutation Taster		=94/6	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: rs111964119; hg19: chr4-15009028;