rs1384313

Variant names:

• chr3-129177231-C-T
• rs1384313
• NM_003418.5:c.-14-5460G>A

Variant summary

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

The NM_003418.5(CNBP):​c.-14-5460G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,224 control chromosomes in the GnomAD database, including 61,419 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 0.89 (61419 hom., cov: 32)
• Consequence: CNBP NM_003418.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 3 publications found

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]

CNBP Gene-Disease associations (from GenCC):

• myotonic dystrophy type 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNBP	NM_003418.5	c.-14-5460G>A		intron_variant	Intron 1 of 4	ENST00000422453.7	NP_003409.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNBP	ENST00000422453.7	c.-14-5460G>A		intron_variant	Intron 1 of 4	1	NM_003418.5	ENSP00000410619.3
CNBP	ENST00000441626.6	c.-14-5460G>A		intron_variant	Intron 1 of 4	2		ENSP00000410769.2
CNBP	ENST00000451728.6	c.-14-5460G>A		intron_variant	Intron 1 of 4	1		ENSP00000399488.2
CNBP	ENST00000446936.6	c.-14-5460G>A		intron_variant	Intron 1 of 4	1		ENSP00000400444.2

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135797 AN: 152106 Hom.: 61410 Cov.: 32

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.892 AC: 135843 AN: 152224 Hom.: 61419 Cov.: 32 AF XY: 0.891 AC XY: 66305 AN XY: 74428

African (AFR) AF: 0.732 AC: 30347 AN: 41480

American (AMR) AF: 0.913 AC: 13962 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3352 AN: 3472

East Asian (EAS) AF: 0.887 AC: 4602 AN: 5186

South Asian (SAS) AF: 0.847 AC: 4084 AN: 4822

European-Finnish (FIN) AF: 0.954 AC: 10133 AN: 10620

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.974 AC: 66275 AN: 68034

Other (OTH) AF: 0.907 AC: 1915 AN: 2112

Alfa AF: 0.949 Hom.: 40633

Bravo AF: 0.883

Asia WGS AF: 0.848 AC: 2950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.46
DANN	Benign	0.72
PhyloP100		-1.9
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: rs1384313; hg19: chr3-128896074;