rs11079028

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-41974115-G-A
• chr17-41974115-G-C
• chr17-41974115-G-T

Variant summary

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

The NM_033133.5(CNP):​c.*191G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 461,592 control chromosomes in the GnomAD database, including 12,267 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 0.19 (3589 hom., cov: 30)
  • Exomes 𝑓: 0.22 (8678 hom.)
• Consequence: CNP NM_033133.5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033133.5. 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
	CNP	NM_033133.5	MANE Select	c.*191G>A		3_prime_UTR	Exon 4 of 4	NP_149124.3
	CNP	NM_001330216.2		c.*191G>A		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>A		3_prime_UTR	Exon 4 of 4	ENSP00000377470.2
	CNP	ENST00000393888.1	TSL:1	c.*191G>A		3_prime_UTR	Exon 4 of 4	ENSP00000377466.1
	CNP	ENST00000472031.1	TSL:2	c.*634G>A		3_prime_UTR	Exon 3 of 3	ENSP00000467641.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 28811 AN: 149548 Hom.: 3581 Cov.: 30

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.221 AC: 68903 AN: 311934 Hom.: 8678 Cov.: 5 AF XY: 0.221 AC XY: 34859 AN XY: 157906

African (AFR) AF: 0.0529 AC: 443 AN: 8378

American (AMR) AF: 0.346 AC: 3122 AN: 9012

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 1759 AN: 9784

East Asian (EAS) AF: 0.429 AC: 9458 AN: 22044

South Asian (SAS) AF: 0.210 AC: 2445 AN: 11634

European-Finnish (FIN) AF: 0.231 AC: 4553 AN: 19710

Middle Eastern (MID) AF: 0.178 AC: 254 AN: 1430

European-Non Finnish (NFE) AF: 0.203 AC: 43087 AN: 211744

Other (OTH) AF: 0.208 AC: 3782 AN: 18198

GnomAD4 genome AF: 0.193 AC: 28830 AN: 149658 Hom.: 3589 Cov.: 30 AF XY: 0.199 AC XY: 14525 AN XY: 72886

African (AFR) AF: 0.0547 AC: 2209 AN: 40350

American (AMR) AF: 0.348 AC: 5200 AN: 14950

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 632 AN: 3456

East Asian (EAS) AF: 0.398 AC: 2017 AN: 5066

South Asian (SAS) AF: 0.251 AC: 1193 AN: 4750

European-Finnish (FIN) AF: 0.250 AC: 2524 AN: 10088

Middle Eastern (MID) AF: 0.188 AC: 54 AN: 288

European-Non Finnish (NFE) AF: 0.214 AC: 14481 AN: 67738

Other (OTH) AF: 0.199 AC: 411 AN: 2068

Alfa AF: 0.202 Hom.: 3750

Bravo AF: 0.192

Asia WGS AF: 0.300 AC: 1042 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.43
PhyloP100		0.60
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.1
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: rs11079028; hg19: chr17-40126133; COSMIC: COSV57270841; COSMIC: COSV57270841;