4-182896818-A-G

Variant names:

• chr4-182896818-A-G
• rs17074237
• NM_001921.3:c.245-2213T>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.245-2213T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0724 in 152,254 control chromosomes in the GnomAD database, including 478 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 0.072 (478 hom., cov: 32)
• Consequence: DCTD NM_001921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351
• Publications: 3 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]

ENSG00000303565 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCTD	NM_001921.3	c.245-2213T>C		intron_variant	Intron 3 of 5	ENST00000438320.7	NP_001912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCTD	ENST00000438320.7	c.245-2213T>C		intron_variant	Intron 3 of 5	1	NM_001921.3	ENSP00000398194.2

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 11007 AN: 152136 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0540

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0530

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

GnomAD4 genome AF: 0.0724 AC: 11025 AN: 152254 Hom.: 478 Cov.: 32 AF XY: 0.0692 AC XY: 5150 AN XY: 74428

African (AFR) AF: 0.125 AC: 5174 AN: 41530

American (AMR) AF: 0.0539 AC: 825 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5194

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4818

European-Finnish (FIN) AF: 0.0417 AC: 442 AN: 10598

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0609 AC: 4141 AN: 68022

Other (OTH) AF: 0.0525 AC: 111 AN: 2116

Alfa AF: 0.0709 Hom.: 388

Bravo AF: 0.0748

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.35
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: rs17074237; hg19: chr4-183817971;