chr5-173890203-C-A

Variant names:

• chr5-173890203-C-A
• rs149568017
• NM_030627.4:c.470C>A

Variant summary

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

The NM_030627.4(CPEB4):​c.470C>A​(p.Pro157His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000785 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00082 (0 hom.)
• Consequence: CPEB4 NM_030627.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 7 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04872608).
• BS2: High AC in GnomAd4 at 74 AD gene.

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.470C>A	p.Pro157His	missense	Exon 1 of 10	NP_085130.2	Q17RY0-1
	CPEB4	NM_001308189.2		c.470C>A	p.Pro157His	missense	Exon 1 of 9	NP_001295118.1	Q17RY0-2
	CPEB4	NM_001308191.2		c.470C>A	p.Pro157His	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.470C>A	p.Pro157His	missense	Exon 1 of 10	ENSP00000265085.5	Q17RY0-1
	CPEB4	ENST00000334035.9	TSL:1	c.470C>A	p.Pro157His	missense	Exon 1 of 9	ENSP00000334533.5	Q17RY0-2
	CPEB4	ENST00000520867.5	TSL:1	c.470C>A	p.Pro157His	missense	Exon 1 of 8	ENSP00000429092.1	B7ZLQ8

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000926

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000541 AC: 136 AN: 251222 AF XY: 0.000552

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000816 AC: 1193 AN: 1461846 Hom.: 0 Cov.: 33 AF XY: 0.000737 AC XY: 536 AN XY: 727220

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00102 AC: 1130 AN: 1112000

Other (OTH) AF: 0.000745 AC: 45 AN: 60396

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.000417 AC XY: 31 AN XY: 74338

African (AFR) AF: 0.000193 AC: 8 AN: 41452

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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

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

European-Non Finnish (NFE) AF: 0.000926 AC: 63 AN: 68032

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000793 Hom.: 0

Bravo AF: 0.000476

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00174 AC: 15

ExAC AF: 0.000626 AC: 76

EpiCase AF: 0.000763

EpiControl AF: 0.00119

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	-0.36	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.6
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.19	T
Polyphen		0.39	B
Vest4		0.28
MVP		0.30
MPC		0.56
ClinPred		0.054	T
GERP RS		5.8
PromoterAI		-0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.29
Mutation Taster		=66/34	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: rs149568017; hg19: chr5-173317206;