rs2072671

Variant names:

• chr1-20589208-A-C
• rs2072671
• NM_001785.3:c.79A>C

Variant summary

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

The NM_001785.3(CDA):​c.79A>C​(p.Lys27Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,613,834 control chromosomes in the GnomAD database, including 83,703 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (5858 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77845 hom.)
• Consequence: CDA NM_001785.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 172 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013175309).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDA	NM_001785.3	c.79A>C	p.Lys27Gln	missense_variant	Exon 1 of 4	ENST00000375071.4	NP_001776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDA	ENST00000375071.4	c.79A>C	p.Lys27Gln	missense_variant	Exon 1 of 4	1	NM_001785.3	ENSP00000364212.3
CDA	ENST00000461985.1	n.123A>C		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38180 AN: 152016 Hom.: 5856 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.279

GnomAD2 exomes AF: 0.280 AC: 70170 AN: 250962 AF XY: 0.284

Gnomad AFR exome AF: 0.0854

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.433

Gnomad EAS exome AF: 0.119

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.319 AC: 466507 AN: 1461700 Hom.: 77845 Cov.: 40 AF XY: 0.318 AC XY: 231105 AN XY: 727154

African (AFR) AF: 0.0828 AC: 2772 AN: 33480

American (AMR) AF: 0.297 AC: 13283 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 11256 AN: 26132

East Asian (EAS) AF: 0.162 AC: 6450 AN: 39698

South Asian (SAS) AF: 0.223 AC: 19233 AN: 86258

European-Finnish (FIN) AF: 0.199 AC: 10617 AN: 53394

Middle Eastern (MID) AF: 0.375 AC: 2164 AN: 5768

European-Non Finnish (NFE) AF: 0.344 AC: 382184 AN: 1111864

Other (OTH) AF: 0.307 AC: 18548 AN: 60386

GnomAD4 genome AF: 0.251 AC: 38186 AN: 152134 Hom.: 5858 Cov.: 32 AF XY: 0.245 AC XY: 18253 AN XY: 74358

African (AFR) AF: 0.0913 AC: 3792 AN: 41516

American (AMR) AF: 0.317 AC: 4857 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3472

East Asian (EAS) AF: 0.140 AC: 723 AN: 5168

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4822

European-Finnish (FIN) AF: 0.210 AC: 2223 AN: 10600

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.338 AC: 22948 AN: 67954

Other (OTH) AF: 0.275 AC: 580 AN: 2106

Alfa AF: 0.320 Hom.: 41009

Bravo AF: 0.253

TwinsUK AF: 0.346 AC: 1283

ALSPAC AF: 0.332 AC: 1279

ESP6500AA AF: 0.103 AC: 456

ESP6500EA AF: 0.346 AC: 2978

ExAC AF: 0.276 AC: 33449

Asia WGS AF: 0.191 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.089
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.055
Sift	Benign	0.31	T
Sift4G	Benign	0.53	T
Polyphen		0.0040	B
Vest4		0.14
MPC		0.081
ClinPred		0.0037	T
GERP RS		4.0
PromoterAI		-0.16	Neutral
Varity_R		0.12
gMVP		0.48
Mutation Taster		=86/14	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2072671; hg19: chr1-20915701; COSMIC: COSV66751560;