chr4-182915337-C-T

Variant names:

• chr4-182915337-C-T
• rs11730323
• NM_001921.3:c.108+124G>A

Variant summary

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

The NM_001921.3(DCTD):​c.108+124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 766,396 control chromosomes in the GnomAD database, including 15,728 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 0.17 (2359 hom., cov: 33)
  • Exomes 𝑓: 0.20 (13369 hom.)
• Consequence: DCTD NM_001921.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826
• Publications: 7 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCTD	NM_001921.3	c.108+124G>A		intron_variant	Intron 2 of 5	ENST00000438320.7	NP_001912.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCTD	ENST00000438320.7	c.108+124G>A		intron_variant	Intron 2 of 5	1	NM_001921.3	ENSP00000398194.2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25489 AN: 152094 Hom.: 2360 Cov.: 33

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.205 AC: 125807 AN: 614184 Hom.: 13369 AF XY: 0.204 AC XY: 66597 AN XY: 325970

African (AFR) AF: 0.0860 AC: 1426 AN: 16574

American (AMR) AF: 0.138 AC: 4032 AN: 29156

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 2537 AN: 16528

East Asian (EAS) AF: 0.232 AC: 8234 AN: 35452

South Asian (SAS) AF: 0.174 AC: 9833 AN: 56470

European-Finnish (FIN) AF: 0.199 AC: 8407 AN: 42172

Middle Eastern (MID) AF: 0.155 AC: 611 AN: 3954

European-Non Finnish (NFE) AF: 0.221 AC: 84452 AN: 381778

Other (OTH) AF: 0.195 AC: 6275 AN: 32100

GnomAD4 genome AF: 0.167 AC: 25484 AN: 152212 Hom.: 2359 Cov.: 33 AF XY: 0.167 AC XY: 12407 AN XY: 74406

African (AFR) AF: 0.0830 AC: 3450 AN: 41556

American (AMR) AF: 0.136 AC: 2085 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 490 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1344 AN: 5156

South Asian (SAS) AF: 0.175 AC: 845 AN: 4826

European-Finnish (FIN) AF: 0.182 AC: 1934 AN: 10602

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14795 AN: 67994

Other (OTH) AF: 0.156 AC: 331 AN: 2116

Alfa AF: 0.199 Hom.: 3250

Bravo AF: 0.162

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.27
DANN	Benign	0.79
PhyloP100		-0.83
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: rs11730323; hg19: chr4-183836490; COSMIC: COSV63866699; COSMIC: COSV63866699;