rs372164501

Variant names:

• chr15-82647861-G-A
• rs372164501
• ENST00000615198.4:c.10C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001365243.1(CPEB1):​c.10C>T​(p.Pro4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,270,462 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (4 hom.)
• Consequence: CPEB1 NM_001365243.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.368
• 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]

CPEB1-AS1 (HGNC:27523): (CPEB1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037144423).
• BS2: High AC in GnomAd4 at 152 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365243.1. 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_001365243.1		c.10C>T	p.Pro4Ser	missense	Exon 1 of 12	NP_001352172.1
	CPEB1	NM_030594.5		c.10C>T	p.Pro4Ser	missense	Exon 1 of 12	NP_085097.3
	CPEB1	NM_001387070.1		c.-274C>T		5_prime_UTR	Exon 1 of 13	NP_001373999.1	Q9BZB8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB1	ENST00000615198.4	TSL:1	c.10C>T	p.Pro4Ser	missense	Exon 1 of 12	ENSP00000477715.1	Q9BZB8-3
	CPEB1-AS1	ENST00000560650.1	TSL:1	n.92G>A		non_coding_transcript_exon	Exon 1 of 4
	CPEB1	ENST00000563519.1	TSL:4	n.159+359C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00100 AC: 152 AN: 151836 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000588 AC: 1 AN: 1702 AF XY: 0.000969

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: 0.00114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00153 AC: 1716 AN: 1118520 Hom.: 4 Cov.: 30 AF XY: 0.00154 AC XY: 825 AN XY: 536556

African (AFR) AF: 0.000175 AC: 4 AN: 22918

American (AMR) AF: 0.000232 AC: 2 AN: 8628

Ashkenazi Jewish (ASJ) AF: 0.0122 AC: 179 AN: 14712

East Asian (EAS) AF: 0.00 AC: 0 AN: 26402

South Asian (SAS) AF: 0.000125 AC: 4 AN: 32050

European-Finnish (FIN) AF: 0.0000425 AC: 1 AN: 23542

Middle Eastern (MID) AF: 0.000290 AC: 1 AN: 3454

European-Non Finnish (NFE) AF: 0.00151 AC: 1421 AN: 942140

Other (OTH) AF: 0.00233 AC: 104 AN: 44674

GnomAD4 genome AF: 0.00100 AC: 152 AN: 151942 Hom.: 0 Cov.: 33 AF XY: 0.000983 AC XY: 73 AN XY: 74290

African (AFR) AF: 0.000361 AC: 15 AN: 41512

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00133 AC: 90 AN: 67862

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00135 Hom.: 0

Bravo AF: 0.00111

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00162 AC: 7

ExAC AF: 0.000306 AC: 5

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	0.078
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.96
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.37
PrimateAI	Uncertain	0.52	T
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.063
MVP		0.15
ClinPred		0.036	T
GERP RS		1.1
PromoterAI		0.064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.077
Mutation Taster		=98/2	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: rs372164501; hg19: chr15-83316612;