rs3886768

Positions:

• chr4-182896171-G-A

Variant summary

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

The NM_001921.3(DCTD):​c.245-1566C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,030 control chromosomes in the GnomAD database, including 3,099 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 0.19 (3099 hom., cov: 33)
• Consequence: DCTD NM_001921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTD	NM_001921.3	c.245-1566C>T		intron_variant		ENST00000438320.7	NP_001912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTD	ENST00000438320.7	c.245-1566C>T		intron_variant		1	NM_001921.3	ENSP00000398194.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29441 AN: 151912 Hom.: 3101 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.194 AC: 29448 AN: 152030 Hom.: 3099 Cov.: 33 AF XY: 0.192 AC XY: 14268 AN XY: 74292

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.180

Alfa AF: 0.204 Hom.: 640

Bravo AF: 0.183

Asia WGS AF: 0.224 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.56
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3886768; hg19: chr4-183817324;