3-129183756-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003418.5(CNBP):c.-15+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,858 control chromosomes in the GnomAD database, including 17,690 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 0.45 (17580 hom., cov: 34)
  • Exomes 𝑓: 0.54 (110 hom.)
• Consequence: CNBP NM_003418.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

Genes affected

CNBP (HGNC:13164): (CCHC-type zinc finger nucleic acid binding protein) This gene encodes a nucleic-acid binding protein with seven zinc-finger domains. The protein has a preference for binding single stranded DNA and RNA. The protein functions in cap-independent translation of ornithine decarboxylase mRNA, and may also function in sterol-mediated transcriptional regulation. A CCTG expansion from <30 repeats to 75-11000 repeats in the first intron of this gene results in myotonic dystrophy type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNBP	NM_003418.5	c.-15+20C>A		intron_variant		ENST00000422453.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNBP	ENST00000422453.7	c.-15+20C>A		intron_variant		1	NM_003418.5

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68703 AN: 152058 Hom.: 17574 Cov.: 34

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.541 AC: 370 AN: 684 Hom.: 110 Cov.: 0 AF XY: 0.578 AC XY: 266 AN XY: 460

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.452 AC: 68711 AN: 152174 Hom.: 17580 Cov.: 34 AF XY: 0.457 AC XY: 33973 AN XY: 74390

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.484

Alfa AF: 0.487 Hom.: 2346

Bravo AF: 0.440

Asia WGS AF: 0.520 AC: 1809 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.65
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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

Publications

LitVar

Other links and lift over

dbSNP: rs1871922; hg19: chr3-128902599;