17-41974115-G-C

Variant names:

• chr17-41974115-G-C
• rs11079028
• NM_033133.5:c.*191G>C

Variant summary

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

The ENST00000393892.8(CNP):​c.*191G>C variant causes a 3 prime UTR 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: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNP ENST00000393892.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605
• Publications: 18 publications found

Genes affected

CNP (HGNC:2158): (2',3'-cyclic nucleotide 3' phosphodiesterase) Predicted to enable 2',3'-cyclic-nucleotide 3'-phosphodiesterase activity. Involved in substantia nigra development. Located in several cellular components, including extracellular space; microtubule; and plasma membrane. Implicated in hypomyelinating leukodystrophy 20; multiple sclerosis; and schizophrenia. Biomarker of alcoholic liver cirrhosis; multiple sclerosis; and restless legs syndrome. [provided by Alliance of Genome Resources, Apr 2022]

CNP Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 20

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393892.8. 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
	CNP	NM_033133.5	MANE Select	c.*191G>C		3_prime_UTR	Exon 4 of 4	NP_149124.3
	CNP	NM_001330216.2		c.*191G>C		3_prime_UTR	Exon 4 of 4	NP_001317145.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNP	ENST00000393892.8	TSL:1 MANE Select	c.*191G>C		3_prime_UTR	Exon 4 of 4	ENSP00000377470.2
	CNP	ENST00000393888.1	TSL:1	c.*191G>C		3_prime_UTR	Exon 4 of 4	ENSP00000377466.1
	CNP	ENST00000472031.1	TSL:2	c.*634G>C		3_prime_UTR	Exon 3 of 3	ENSP00000467641.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 312484 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 158198

African (AFR) AF: 0.00 AC: 0 AN: 8382

American (AMR) AF: 0.00 AC: 0 AN: 9028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9798

East Asian (EAS) AF: 0.00 AC: 0 AN: 22114

South Asian (SAS) AF: 0.00 AC: 0 AN: 11654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1430

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 212130

Other (OTH) AF: 0.00 AC: 0 AN: 18218

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 3750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.42
PhyloP100		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11079028; hg19: chr17-40126133;