chr15-82556112-C-T

Variant names:

• chr15-82556112-C-T
• rs1361276650
• NM_001365242.1:c.698G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001365242.1(CPEB1):​c.698G>A​(p.Arg233His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,602,552 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CPEB1 NM_001365242.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.42
• Publications: 0 publications found

Genes affected

CPEB1 (HGNC:21744): (cytoplasmic polyadenylation element binding protein 1) This gene encodes a member of the cytoplasmic polyadenylation element binding protein family. This highly conserved protein binds to a specific RNA sequence, called the cytoplasmic polyadenylation element, found in the 3' untranslated region of some mRNAs. The encoded protein functions in both the cytoplasm and the nucleus. It is involved in the regulation of mRNA translation, as well as processing of the 3' untranslated region, and may play a role in cell proliferation and tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ENSG00000260836 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 31 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365242.1. 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
	CPEB1	NM_001365242.1	MANE Select	c.698G>A	p.Arg233His	missense	Exon 6 of 13	NP_001352171.1	A0A087WXG7
	CPEB1	NM_001387061.1		c.698G>A	p.Arg233His	missense	Exon 8 of 15	NP_001373990.1
	CPEB1	NM_001365240.1		c.698G>A	p.Arg233His	missense	Exon 6 of 13	NP_001352169.1	A0A087WXG7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB1	ENST00000684509.1	MANE Select	c.698G>A	p.Arg233His	missense	Exon 6 of 13	ENSP00000507835.1	A0A087WXG7
	CPEB1	ENST00000617958.4	TSL:1	c.797G>A	p.Arg266His	missense	Exon 5 of 12	ENSP00000478598.1	A0A024R214
	ENSG00000260836	ENST00000562833.2	TSL:3	c.392G>A	p.Arg131His	missense	Exon 3 of 13	ENSP00000454786.2	H3BNC9

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152052 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD2 exomes AF: 0.00000422 AC: 1 AN: 237054 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: 0.00000916

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000214 AC: 31 AN: 1450500 Hom.: 0 Cov.: 31 AF XY: 0.0000166 AC XY: 12 AN XY: 721120

African (AFR) AF: 0.00 AC: 0 AN: 33002

American (AMR) AF: 0.00 AC: 0 AN: 42258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25848

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39246

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000262 AC: 29 AN: 1107854

Other (OTH) AF: 0.00 AC: 0 AN: 60048

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152052 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74250

African (AFR) AF: 0.0000242 AC: 1 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000113

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	0.22
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.057	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0033	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.4
PrimateAI	Pathogenic	0.80	T
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.29		Loss of solvent accessibility (P = 0.0079)
MVP		0.82
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.47
Mutation Taster		=214/86	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: -36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1361276650; hg19: chr15-83224862;