4-182892272-C-T

Position:

• chr4-182892272-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.458+759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,114 control chromosomes in the GnomAD database, including 2,188 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 0.16 (2188 hom., cov: 33)
• Consequence: DCTD NM_001921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTD	NM_001921.3	c.458+759G>A		intron_variant		ENST00000438320.7	NP_001912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTD	ENST00000438320.7	c.458+759G>A		intron_variant		1	NM_001921.3	ENSP00000398194.2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23691 AN: 151996 Hom.: 2183 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.156 AC: 23716 AN: 152114 Hom.: 2188 Cov.: 33 AF XY: 0.156 AC XY: 11607 AN XY: 74360

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0988

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.160

Alfa AF: 0.123 Hom.: 1799

Bravo AF: 0.167

Asia WGS AF: 0.267 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.2
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: rs12507552; hg19: chr4-183813425;