chr5-173889839-A-C

Variant names:

• chr5-173889839-A-C
• NM_030627.4:c.106A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030627.4(CPEB4):​c.106A>C​(p.Asn36His) 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: 8.91
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2735495).

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.106A>C	p.Asn36His	missense	Exon 1 of 10	NP_085130.2	Q17RY0-1
	CPEB4	NM_001308189.2		c.106A>C	p.Asn36His	missense	Exon 1 of 9	NP_001295118.1	Q17RY0-2
	CPEB4	NM_001308191.2		c.106A>C	p.Asn36His	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.106A>C	p.Asn36His	missense	Exon 1 of 10	ENSP00000265085.5	Q17RY0-1
	CPEB4	ENST00000334035.9	TSL:1	c.106A>C	p.Asn36His	missense	Exon 1 of 9	ENSP00000334533.5	Q17RY0-2
	CPEB4	ENST00000520867.5	TSL:1	c.106A>C	p.Asn36His	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	0.10
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.1	L
PhyloP100		8.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.23
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.28	T
Polyphen		0.94	P
Vest4		0.50
MutPred		0.15		Loss of solvent accessibility (P = 0.0155)
MVP		0.64
MPC		1.0
ClinPred		0.79	D
GERP RS		5.6
PromoterAI		-0.024	Neutral
Varity_R		0.41
gMVP		0.35
Mutation Taster		=84/16	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: chr5-173316842;