rs11730323

chr4-182915337-C-T

Variant summary

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

The NM_001921.3(DCTD):c.108+124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 766,396 control chromosomes in the GnomAD database, including 15,728 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 0.17 (2359 hom., cov: 33)
  • Exomes 𝑓: 0.20 (13369 hom.)
• Consequence: DCTD NM_001921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCTD	NM_001921.3	c.108+124G>A		intron_variant		ENST00000438320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCTD	ENST00000438320.7	c.108+124G>A		intron_variant		1	NM_001921.3	P1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25489 AN: 152094 Hom.: 2360 Cov.: 33

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.205 AC: 125807 AN: 614184 Hom.: 13369 AF XY: 0.204 AC XY: 66597 AN XY: 325970

Gnomad4 AFR exome AF: 0.0860

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.167 AC: 25484 AN: 152212 Hom.: 2359 Cov.: 33 AF XY: 0.167 AC XY: 12407 AN XY: 74406

Gnomad4 AFR AF: 0.0830

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.156

Alfa AF: 0.201 Hom.: 2296

Bravo AF: 0.162

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.27
Dann	Benign	0.79

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: rs11730323; hg19: chr4-183836490; COSMIC: COSV63866699; COSMIC: COSV63866699;