NM_030627.4:c.1258+2955G>A

Variant names:

• chr5-173935455-G-A
• rs6861681
• NM_030627.4:c.1258+2955G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030627.4(CPEB4):​c.1258+2955G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,068 control chromosomes in the GnomAD database, including 4,967 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4967 hom., cov: 33)
• Consequence: CPEB4 NM_030627.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 71 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPEB4	NM_030627.4	c.1258+2955G>A		intron_variant	Intron 3 of 9	ENST00000265085.10	NP_085130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB4	ENST00000265085.10	c.1258+2955G>A		intron_variant	Intron 3 of 9	1	NM_030627.4	ENSP00000265085.5

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33777 AN: 151950 Hom.: 4969 Cov.: 33

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0804

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.190

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33765 AN: 152068 Hom.: 4967 Cov.: 33 AF XY: 0.225 AC XY: 16742 AN XY: 74328

African (AFR) AF: 0.0669 AC: 2776 AN: 41502

American (AMR) AF: 0.185 AC: 2835 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3470

East Asian (EAS) AF: 0.0800 AC: 414 AN: 5176

South Asian (SAS) AF: 0.107 AC: 517 AN: 4828

European-Finnish (FIN) AF: 0.456 AC: 4804 AN: 10528

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20730 AN: 67962

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.272 Hom.: 18605

Bravo AF: 0.196

Asia WGS AF: 0.0860 AC: 301 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.30
DANN	Benign	0.40
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs6861681; hg19: chr5-173362458;