10-14820043-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001029954.3(CDNF):c.501T>C(p.Tyr167=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,614,060 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (37 hom.)
• Consequence: CDNF NM_001029954.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.396

Genes affected

CDNF (HGNC:24913): (cerebral dopamine neurotrophic factor) Predicted to enable growth factor activity. Predicted to be involved in dopaminergic neuron differentiation and neuron projection development. Predicted to be active in endoplasmic reticulum and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 10-14820043-A-G is Benign according to our data. Variant chr10-14820043-A-G is described in ClinVar as [Benign]. Clinvar id is 786148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.396 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDNF	NM_001029954.3	c.501T>C	p.Tyr167=	synonymous_variant	4/4	ENST00000465530.2
CDNF	XM_011519488.3	c.528T>C	p.Tyr176=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDNF	ENST00000465530.2	c.501T>C	p.Tyr167=	synonymous_variant	4/4	1	NM_001029954.3	P1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2186 AN: 152104 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00760

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00379 AC: 952 AN: 251468 Hom.: 17 AF XY: 0.00276 AC XY: 375 AN XY: 135904

Gnomad AFR exome AF: 0.0516

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000791

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00151 AC: 2202 AN: 1461838 Hom.: 37 Cov.: 31 AF XY: 0.00133 AC XY: 964 AN XY: 727228

Gnomad4 AFR exome AF: 0.0537

Gnomad4 AMR exome AF: 0.00237

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000522

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000297

Gnomad4 OTH exome AF: 0.00354

GnomAD4 genome AF: 0.0144 AC: 2195 AN: 152222 Hom.: 61 Cov.: 32 AF XY: 0.0137 AC XY: 1019 AN XY: 74410

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.00759

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00568 Hom.: 10

Bravo AF: 0.0165

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.022
Dann	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61746971; hg19: chr10-14862042;