rs527912

Positions:

• chr1-20607790-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001785.3(CDA):​c.266+2751G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,098 control chromosomes in the GnomAD database, including 8,699 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 (8699 hom., cov: 32)
• Consequence: CDA NM_001785.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDA	NM_001785.3	c.266+2751G>A		intron_variant		ENST00000375071.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDA	ENST00000375071.4	c.266+2751G>A		intron_variant		1	NM_001785.3	P1
CDA	ENST00000461985.1	n.310+2751G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50888 AN: 151980 Hom.: 8697 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.335 AC: 50903 AN: 152098 Hom.: 8699 Cov.: 32 AF XY: 0.334 AC XY: 24792 AN XY: 74334

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.358

Alfa AF: 0.369 Hom.: 18513

Bravo AF: 0.340

Asia WGS AF: 0.296 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.83

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: rs527912; hg19: chr1-20934283;