4-182900509-T-C

Variant names:

• chr4-182900509-T-C
• rs13114435
• NM_001921.3:c.245-5904A>G

Variant summary

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

The NM_001921.3(DCTD):​c.245-5904A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,834 control chromosomes in the GnomAD database, including 4,434 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 0.23 (4434 hom., cov: 32)
• Consequence: DCTD NM_001921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 10 publications found

Genes affected

DCTD (HGNC:2710): (dCMP deaminase) The protein encoded by this gene catalyzes the deamination of dCMP to dUMP, the nucleotide substrate for thymidylate synthase. The encoded protein is allosterically activated by dCTP and inhibited by dTTP, and is found as a homohexamer. This protein uses zinc as a cofactor for its activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCTD	NM_001921.3	c.245-5904A>G		intron_variant	Intron 3 of 5	ENST00000438320.7	NP_001912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCTD	ENST00000438320.7	c.245-5904A>G		intron_variant	Intron 3 of 5	1	NM_001921.3	ENSP00000398194.2

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34772 AN: 151714 Hom.: 4432 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.229 AC: 34781 AN: 151834 Hom.: 4434 Cov.: 32 AF XY: 0.226 AC XY: 16769 AN XY: 74192

African (AFR) AF: 0.131 AC: 5414 AN: 41398

American (AMR) AF: 0.172 AC: 2619 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1179 AN: 5158

South Asian (SAS) AF: 0.231 AC: 1109 AN: 4808

European-Finnish (FIN) AF: 0.261 AC: 2740 AN: 10496

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20168 AN: 67930

Other (OTH) AF: 0.207 AC: 436 AN: 2106

Alfa AF: 0.261 Hom.: 9252

Bravo AF: 0.216

Asia WGS AF: 0.254 AC: 881 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.072
DANN	Benign	0.54
PhyloP100		-2.5
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: rs13114435; hg19: chr4-183821662;