4-182904718-A-G

Position:

• chr4-182904718-A-G

Variant summary

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

The ENST00000438320.7(DCTD):​c.245-10113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,808 control chromosomes in the GnomAD database, including 8,387 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 (8387 hom., cov: 31)
• Consequence: DCTD ENST00000438320.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTD	NM_001921.3	c.245-10113T>C		intron_variant		ENST00000438320.7	NP_001912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTD	ENST00000438320.7	c.245-10113T>C		intron_variant		1	NM_001921.3	ENSP00000398194	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49823 AN: 151690 Hom.: 8394 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.328 AC: 49826 AN: 151808 Hom.: 8387 Cov.: 31 AF XY: 0.325 AC XY: 24070 AN XY: 74134

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.296

Alfa AF: 0.331 Hom.: 4050

Bravo AF: 0.320

Asia WGS AF: 0.344 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.59

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: rs13116598; hg19: chr4-183825871;