4-182890360-C-T

Position:

• chr4-182890360-C-T

Variant summary

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

The ENST00000438320.7(DCTD):​c.*1039G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,132 control chromosomes in the GnomAD database, including 10,379 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 0.34 (10378 hom., cov: 33)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: DCTD ENST00000438320.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTD	NM_001921.3	c.*1039G>A		3_prime_UTR_variant	6/6	ENST00000438320.7	NP_001912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTD	ENST00000438320.7	c.*1039G>A		3_prime_UTR_variant	6/6	1	NM_001921.3	ENSP00000398194	P1
DCTD	ENST00000357067.7	c.*1039G>A		3_prime_UTR_variant	6/6	1		ENSP00000349576
DCTD	ENST00000500813.6	c.*1314G>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	2		ENSP00000425462
DCTD	ENST00000507543.5	c.*1586G>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000422386

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51467 AN: 151982 Hom.: 10367 Cov.: 33

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.250 AC: 8 AN: 32 Hom.: 1 Cov.: 0 AF XY: 0.292 AC XY: 7 AN XY: 24

Gnomad4 AFR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.339 AC: 51510 AN: 152100 Hom.: 10378 Cov.: 33 AF XY: 0.336 AC XY: 24958 AN XY: 74354

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.319

Alfa AF: 0.249 Hom.: 6748

Bravo AF: 0.359

Asia WGS AF: 0.317 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.26
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: rs7277; hg19: chr4-183811513;