3-129183756-G-C

Variant names:

• chr3-129183756-G-C
• rs1871922
• NM_003418.5:c.-15+20C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003418.5(CNBP):​c.-15+20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
• Consequence: CNBP NM_003418.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 10 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

ENSG00000289469 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003418.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNBP	NM_003418.5	MANE Select	c.-15+20C>G		intron	N/A	NP_003409.1
	CNBP	NM_001127192.2		c.-15+20C>G		intron	N/A	NP_001120664.1
	CNBP	NM_001127193.2		c.-15+20C>G		intron	N/A	NP_001120665.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNBP	ENST00000422453.7	TSL:1 MANE Select	c.-15+20C>G		intron	N/A	ENSP00000410619.3
	CNBP	ENST00000441626.6	TSL:2	c.-15+20C>G		intron	N/A	ENSP00000410769.2
	CNBP	ENST00000451728.6	TSL:1	c.-15+20C>G		intron	N/A	ENSP00000399488.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 2346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.0
DANN	Benign	0.60
PhyloP100		-2.8
PromoterAI		-0.028	Neutral

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: rs1871922; hg19: chr3-128902599;