rs8078650

Variant names:

• chr17-41968753-T-G
• rs8078650
• NM_033133.5:c.676+13T>G

Your query was ambiguous. Multiple possible variants found:

• chr17-41968753-T-G
• chr17-41968753-T-A

Variant summary

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

The NM_033133.5(CNP):​c.676+13T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,597,050 control chromosomes in the GnomAD database, including 29,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (3954 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25291 hom.)
• Consequence: CNP NM_033133.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• Publications: 22 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNP	NM_033133.5	MANE Select	c.676+13T>G		intron	N/A	NP_149124.3
	CNP	NM_001330216.2		c.616+13T>G		intron	N/A	NP_001317145.1	P09543-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNP	ENST00000393892.8	TSL:1 MANE Select	c.676+13T>G		intron	N/A	ENSP00000377470.2	P09543-1
	CNP	ENST00000393888.1	TSL:1	c.616+13T>G		intron	N/A	ENSP00000377466.1	P09543-2
	CNP	ENST00000472031.1	TSL:2	c.3+1866T>G		intron	N/A	ENSP00000467641.1	K7EQ27

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32463 AN: 151994 Hom.: 3933 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.176 AC: 41145 AN: 233798 AF XY: 0.175

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.0775

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.175

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.182 AC: 263227 AN: 1444938 Hom.: 25291 Cov.: 32 AF XY: 0.181 AC XY: 129503 AN XY: 716996

African (AFR) AF: 0.329 AC: 10782 AN: 32818

American (AMR) AF: 0.0824 AC: 3539 AN: 42928

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 2971 AN: 25234

East Asian (EAS) AF: 0.154 AC: 6054 AN: 39372

South Asian (SAS) AF: 0.164 AC: 13843 AN: 84650

European-Finnish (FIN) AF: 0.249 AC: 13055 AN: 52526

Middle Eastern (MID) AF: 0.108 AC: 615 AN: 5692

European-Non Finnish (NFE) AF: 0.183 AC: 201544 AN: 1102182

Other (OTH) AF: 0.182 AC: 10824 AN: 59536

GnomAD4 genome AF: 0.214 AC: 32527 AN: 152112 Hom.: 3954 Cov.: 32 AF XY: 0.213 AC XY: 15835 AN XY: 74350

African (AFR) AF: 0.321 AC: 13301 AN: 41478

American (AMR) AF: 0.114 AC: 1748 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3470

East Asian (EAS) AF: 0.170 AC: 880 AN: 5172

South Asian (SAS) AF: 0.170 AC: 818 AN: 4824

European-Finnish (FIN) AF: 0.258 AC: 2723 AN: 10570

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12113 AN: 68000

Other (OTH) AF: 0.195 AC: 411 AN: 2112

Alfa AF: 0.182 Hom.: 1832

Bravo AF: 0.207

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.2
DANN	Benign	0.62
PhyloP100		0.68
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8078650; hg19: chr17-40120771; COSMIC: COSV66368059; COSMIC: COSV66368059;