4-182904718-A-G

Variant names:

• chr4-182904718-A-G
• rs13116598
• NM_001921.3:c.245-10113T>C

Variant summary

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

The NM_001921.3(DCTD):​c.245-10113T>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 NM_001921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001921.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCTD	NM_001921.3	MANE Select	c.245-10113T>C		intron	N/A	NP_001912.2
	DCTD	NM_001012732.2		c.278-10113T>C		intron	N/A	NP_001012750.1
	DCTD	NM_001351743.2		c.245-10113T>C		intron	N/A	NP_001338672.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCTD	ENST00000438320.7	TSL:1 MANE Select	c.245-10113T>C		intron	N/A	ENSP00000398194.2
	DCTD	ENST00000357067.7	TSL:1	c.278-10113T>C		intron	N/A	ENSP00000349576.3
	DCTD	ENST00000507631.5	TSL:1	n.109-10113T>C		intron	N/A	ENSP00000425287.1

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

African (AFR) AF: 0.317 AC: 13117 AN: 41406

American (AMR) AF: 0.210 AC: 3210 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3472

East Asian (EAS) AF: 0.352 AC: 1801 AN: 5116

South Asian (SAS) AF: 0.301 AC: 1449 AN: 4806

European-Finnish (FIN) AF: 0.331 AC: 3486 AN: 10538

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24776 AN: 67906

Other (OTH) AF: 0.296 AC: 624 AN: 2106

Alfa AF: 0.335 Hom.: 6062

Bravo AF: 0.320

Asia WGS AF: 0.344 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.59
PhyloP100		-2.6
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: rs13116598; hg19: chr4-183825871;