3-129172734-T-A

Position:

• chr3-129172734-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003418.5(CNBP):​c.-14-963A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 110,990 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0017 (1 hom., cov: 30)
• Consequence: CNBP NM_003418.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.591

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-129172734-T-A is Benign according to our data. Variant chr3-129172734-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3030076.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00175 (194/110990) while in subpopulation SAS AF= 0.0374 (116/3102). AF 95% confidence interval is 0.0319. There are 1 homozygotes in gnomad4. There are 128 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 194 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNBP	NM_003418.5	c.-14-963A>T		intron_variant		ENST00000422453.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNBP	ENST00000422453.7	c.-14-963A>T		intron_variant		1	NM_003418.5

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 194 AN: 110872 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.000931

Gnomad AMI AF: 0.00698

Gnomad AMR AF: 0.000920

Gnomad ASJ AF: 0.000393

Gnomad EAS AF: 0.000290

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000599

Gnomad OTH AF: 0.000652

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

GnomAD4 genome AF: 0.00175 AC: 194 AN: 110990 Hom.: 1 Cov.: 30 AF XY: 0.00239 AC XY: 128 AN XY: 53558

Gnomad4 AFR AF: 0.000928

Gnomad4 AMR AF: 0.000918

Gnomad4 ASJ AF: 0.000393

Gnomad4 EAS AF: 0.000290

Gnomad4 SAS AF: 0.0374

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000599

Gnomad4 OTH AF: 0.000645

Alfa AF: 0.00118 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CNBP-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.50

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: rs867362489; hg19: chr3-128891577;