NM_030627.4:c.1207+246T>G

Variant names:

• chr5-173910850-T-G
• rs17695092
• NM_030627.4:c.1207+246T>G

Variant summary

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

The NM_030627.4(CPEB4):​c.1207+246T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 429,050 control chromosomes in the GnomAD database, including 15,947 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 (4958 hom., cov: 31)
  • Exomes 𝑓: 0.26 (10989 hom.)
• Consequence: CPEB4 NM_030627.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 54 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=-0.89).
• 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.1207+246T>G		intron_variant	Intron 2 of 9	ENST00000265085.10	NP_085130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPEB4	ENST00000265085.10	c.1207+246T>G		intron_variant	Intron 2 of 9	1	NM_030627.4	ENSP00000265085.5

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33759 AN: 151964 Hom.: 4959 Cov.: 31

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.263 AC: 72823 AN: 276968 Hom.: 10989 Cov.: 0 AF XY: 0.257 AC XY: 37045 AN XY: 144250

African (AFR) AF: 0.0697 AC: 523 AN: 7502

American (AMR) AF: 0.173 AC: 1575 AN: 9114

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 2722 AN: 9556

East Asian (EAS) AF: 0.0879 AC: 1820 AN: 20696

South Asian (SAS) AF: 0.113 AC: 2109 AN: 18588

European-Finnish (FIN) AF: 0.409 AC: 8209 AN: 20090

Middle Eastern (MID) AF: 0.212 AC: 289 AN: 1364

European-Non Finnish (NFE) AF: 0.297 AC: 51313 AN: 172766

Other (OTH) AF: 0.247 AC: 4263 AN: 17292

GnomAD4 genome AF: 0.222 AC: 33748 AN: 152082 Hom.: 4958 Cov.: 31 AF XY: 0.225 AC XY: 16729 AN XY: 74332

African (AFR) AF: 0.0667 AC: 2770 AN: 41512

American (AMR) AF: 0.185 AC: 2832 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3468

East Asian (EAS) AF: 0.0808 AC: 419 AN: 5188

South Asian (SAS) AF: 0.107 AC: 517 AN: 4818

European-Finnish (FIN) AF: 0.455 AC: 4794 AN: 10532

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

European-Non Finnish (NFE) AF: 0.305 AC: 20728 AN: 67956

Other (OTH) AF: 0.188 AC: 398 AN: 2112

Alfa AF: 0.260 Hom.: 8094

Bravo AF: 0.196

Asia WGS AF: 0.0880 AC: 306 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.63
PhyloP100		-0.47
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: rs17695092; hg19: chr5-173337853;