Genetic Variant NM_001785.3:c.208G>A (chr1-20604981-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

63 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

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

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 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 GnomAdExome4. There are 358 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDA	NM_001785.3 link	c.208G>A	p.Ala70Thr	missense_variant	Exon 2 of 4	ENST00000375071.4	NP_001776.1	P32320

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDA	ENST00000375071.4 link	c.208G>A	p.Ala70Thr	missense_variant	Exon 2 of 4	1	NM_001785.3	ENSP00000364212.3		P32320
CDA	ENST00000461985.1 link	n.252G>A		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.000259

AC:

AN:

251076

AF XY:

0.000243

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 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

African (AFR)

AF:

0.000119

AC:

AN:

33474

American (AMR)

AF:

0.0000224

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0172

AC:

684

AN:

39692

South Asian (SAS)

AF:

0.000104

AC:

AN:

86182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1111852

Other (OTH)

AF:

0.0000828

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

111

148

185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000354

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41584

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00715

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000506

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

(source)

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

PhyloP100

8.9

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

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over