chr1-20618562-C-T

Variant names:

• chr1-20618562-C-T
• rs1048977
• NM_001785.3:c.435C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001785.3(CDA):​c.435C>T​(p.Thr145Thr) 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
• Publications: 70 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001785.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDA	NM_001785.3	MANE Select	c.435C>T	p.Thr145Thr	synonymous	Exon 4 of 4	NP_001776.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDA	ENST00000375071.4	TSL:1 MANE Select	c.435C>T	p.Thr145Thr	synonymous	Exon 4 of 4	ENSP00000364212.3
	CDA	ENST00000461985.1	TSL:3	n.421C>T		non_coding_transcript_exon	Exon 3 of 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

GnomAD2 exomes AF: 0.307 AC: 76987 AN: 250834 AF XY: 0.304

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 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

African (AFR) AF: 0.382 AC: 12483 AN: 32718

American (AMR) AF: 0.311 AC: 13864 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 6256 AN: 25918

East Asian (EAS) AF: 0.267 AC: 10546 AN: 39492

South Asian (SAS) AF: 0.268 AC: 22903 AN: 85598

European-Finnish (FIN) AF: 0.319 AC: 16975 AN: 53292

Middle Eastern (MID) AF: 0.235 AC: 1345 AN: 5718

European-Non Finnish (NFE) AF: 0.323 AC: 349548 AN: 1081728

Other (OTH) AF: 0.311 AC: 18437 AN: 59218

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

African (AFR) AF: 0.385 AC: 15920 AN: 41366

American (AMR) AF: 0.333 AC: 5069 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1319 AN: 5104

South Asian (SAS) AF: 0.261 AC: 1253 AN: 4804

European-Finnish (FIN) AF: 0.314 AC: 3312 AN: 10548

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21732 AN: 67844

Other (OTH) AF: 0.313 AC: 658 AN: 2102

Alfa AF: 0.326 Hom.: 24261

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		1.1
Mutation Taster		=100/0	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: rs1048977; hg19: chr1-20945055; COSMIC: COSV66751489;