10-14820141-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001029954.3(CDNF):c.403G>T(p.Ala135Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00272 in 1,608,798 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict 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 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.28

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020723343).
• BP6: Variant 10-14820141-C-A is Benign according to our data. Variant chr10-14820141-C-A is described in ClinVar as [Benign]. Clinvar id is 786149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDNF	NM_001029954.3	c.403G>T	p.Ala135Ser	missense_variant	4/4	ENST00000465530.2
CDNF	XM_011519488.3	c.430G>T	p.Ala144Ser	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDNF	ENST00000465530.2	c.403G>T	p.Ala135Ser	missense_variant	4/4	1	NM_001029954.3	P1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2186 AN: 152138 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: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00388 AC: 949 AN: 244534 Hom.: 17 AF XY: 0.00284 AC XY: 375 AN XY: 132172

Gnomad AFR exome AF: 0.0518

Gnomad AMR exome AF: 0.00163

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00108

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000805

Gnomad OTH exome AF: 0.00302

GnomAD4 exome AF: 0.00150 AC: 2188 AN: 1456542 Hom.: 37 Cov.: 31 AF XY: 0.00132 AC XY: 956 AN XY: 724490

Gnomad4 AFR exome AF: 0.0537

Gnomad4 AMR exome AF: 0.00244

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000519

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000324

Gnomad4 OTH exome AF: 0.00349

GnomAD4 genome AF: 0.0144 AC: 2195 AN: 152256 Hom.: 61 Cov.: 32 AF XY: 0.0137 AC XY: 1020 AN XY: 74444

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.00759

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00300 Hom.: 15

Bravo AF: 0.0165

ESP6500AA AF: 0.0465 AC: 205

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00467 AC: 567

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
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	17
Dann	Benign	0.70
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.054
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.69	D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.10
MVP		0.15
ClinPred		0.014	T
GERP RS		5.9

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61740068; hg19: chr10-14862140; COSMIC: COSV99058989;