Variant 1-20604981-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_001785.3(CDA):c.208G>A(p.Ala70Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000483 in 1,613,924 control chromosomes in the GnomAD database, including 13 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. Synonymous variant affecting the same amino acid position (i.e. A70A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 11 hom. )

Consequence

CDA
NM_001785.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.94

Variant links:

Genes affected

CDA (HGNC:1712): (cytidine deaminase) This gene encodes an enzyme involved in pyrimidine salvaging. The encoded protein forms a homotetramer that catalyzes the irreversible hydrolytic deamination of cytidine and deoxycytidine to uridine and deoxyuridine, respectively. It is one of several deaminases responsible for maintaining the cellular pyrimidine pool. Mutations in this gene are associated with decreased sensitivity to the cytosine nucleoside analogue cytosine arabinoside used in the treatment of certain childhood leukemias. [provided by RefSeq, Jul 2008]

CDA links:

CDA (HGNC:):

CDA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09961021).

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000496 (725/1461594) while in subpopulation EAS AF= 0.0172 (684/39692). AF 95% confidence interval is 0.0162. There are 11 homozygotes in gnomad4_exome. There are 358 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDA	NM_001785.3 linkuse as main transcript	c.208G>A	p.Ala70Thr	missense_variant	2/4	ENST00000375071.4	NP_001776.1	P32320

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDA	ENST00000375071.4 linkuse as main transcript	c.208G>A	p.Ala70Thr	missense_variant	2/4	1	NM_001785.3	ENSP00000364212.3		P32320
CDA	ENST00000461985.1 linkuse as main transcript	n.252G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00713

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000259

AC:

AN:

251076

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00299

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000496

AC:

725

AN:

1461594

Hom.:

Cov.:

AF XY:

0.000492

AC XY:

358

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0172

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000354

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00715

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000766

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.071

MetaRNN

Benign

0.10

MetaSVM

Uncertain

0.23

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.027

Polyphen

1.0

Vest4

0.80

MVP

0.70

MPC

0.40

ClinPred

0.21

GERP RS

5.8

Varity_R

0.79

gMVP

0.86

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over