chr5-173890106-G-C

Variant names:

• chr5-173890106-G-C
• NM_030627.4:c.373G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030627.4(CPEB4):​c.373G>C​(p.Glu125Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPEB4 NM_030627.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.33
• Publications: 0 publications found

Genes affected

CPEB4 (HGNC:21747): (cytoplasmic polyadenylation element binding protein 4) Enables RNA binding activity. Predicted to be involved in several processes, including cellular response to glucose starvation; negative regulation of cytoplasmic translation; and response to ischemia. Located in cytoplasm and nucleus. Biomarker of liver cirrhosis; portal hypertension; and primary biliary cholangitis. [provided by Alliance of Genome Resources, Apr 2022]

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=0.1790618).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030627.4. 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
	CPEB4	NM_030627.4	MANE Select	c.373G>C	p.Glu125Gln	missense	Exon 1 of 10	NP_085130.2	Q17RY0-1
	CPEB4	NM_001308189.2		c.373G>C	p.Glu125Gln	missense	Exon 1 of 9	NP_001295118.1	Q17RY0-2
	CPEB4	NM_001308191.2		c.373G>C	p.Glu125Gln	missense	Exon 1 of 8	NP_001295120.1	B7ZLQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPEB4	ENST00000265085.10	TSL:1 MANE Select	c.373G>C	p.Glu125Gln	missense	Exon 1 of 10	ENSP00000265085.5	Q17RY0-1
	CPEB4	ENST00000334035.9	TSL:1	c.373G>C	p.Glu125Gln	missense	Exon 1 of 9	ENSP00000334533.5	Q17RY0-2
	CPEB4	ENST00000520867.5	TSL:1	c.373G>C	p.Glu125Gln	missense	Exon 1 of 8	ENSP00000429092.1	B7ZLQ8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.12
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		9.3
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.25
Sift	Benign	0.034	D
Sift4G	Benign	0.45	T
Polyphen		0.67	P
Vest4		0.17
MutPred		0.11		Loss of solvent accessibility (P = 0.0509)
MVP		0.61
MPC		0.51
ClinPred		0.87	D
GERP RS		6.0
Varity_R		0.19
gMVP		0.32
Mutation Taster		=70/30	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

hg19: chr5-173317109;