rs1048977

Positions:

• chr1-20618562-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001785.3(CDA):​c.435C>T​(p.Thr145=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,580,002 control chromosomes in the GnomAD database, including 81,410 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.

• Frequency:
  • Genomes: 𝑓 0.33 (8558 hom., cov: 30)
  • Exomes 𝑓: 0.32 (72852 hom.)
• Consequence: CDA NM_001785.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=1.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDA	NM_001785.3	c.435C>T	p.Thr145=	synonymous_variant	4/4	ENST00000375071.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDA	ENST00000375071.4	c.435C>T	p.Thr145=	synonymous_variant	4/4	1	NM_001785.3	P1
CDA	ENST00000461985.1	n.421C>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50510 AN: 151562 Hom.: 8544 Cov.: 30

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.316

GnomAD3 exomes AF: 0.307 AC: 76987 AN: 250834 Hom.: 12088 AF XY: 0.304 AC XY: 41201 AN XY: 135568

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.237

Gnomad SAS exome AF: 0.265

Gnomad FIN exome AF: 0.322

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.302

GnomAD4 exome AF: 0.317 AC: 452357 AN: 1428322 Hom.: 72852 Cov.: 25 AF XY: 0.315 AC XY: 224241 AN XY: 712566

Gnomad4 AFR exome AF: 0.382

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.323

Gnomad4 OTH exome AF: 0.311

GnomAD4 genome AF: 0.333 AC: 50559 AN: 151680 Hom.: 8558 Cov.: 30 AF XY: 0.331 AC XY: 24522 AN XY: 74110

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.313

Alfa AF: 0.324 Hom.: 8675

Bravo AF: 0.338

Asia WGS AF: 0.260 AC: 905 AN: 3478

EpiCase AF: 0.313

EpiControl AF: 0.314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.5
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs1048977; hg19: chr1-20945055; COSMIC: COSV66751489;