chr4-182912789-A-C

Position:

• chr4-182912789-A-C

Variant summary

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

The NM_001921.3(DCTD):​c.244+2134T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,908 control chromosomes in the GnomAD database, including 17,861 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 0.48 (17861 hom., cov: 32)
• Consequence: DCTD NM_001921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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 (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCTD	NM_001921.3	c.244+2134T>G		intron_variant		ENST00000438320.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCTD	ENST00000438320.7	c.244+2134T>G		intron_variant		1	NM_001921.3	P1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72309 AN: 151788 Hom.: 17837 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.476 AC: 72379 AN: 151908 Hom.: 17861 Cov.: 32 AF XY: 0.474 AC XY: 35185 AN XY: 74252

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.422

Alfa AF: 0.446 Hom.: 31758

Bravo AF: 0.466

Asia WGS AF: 0.385 AC: 1334 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	1.6
DANN	Benign	0.61

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: rs6823077; hg19: chr4-183833942;