4-71028147-C-T

Variant names:

• chr4-71028147-C-T
• rs4694362
• NM_000788.3:c.757-1205C>T

Variant summary

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

The NM_000788.3(DCK):​c.757-1205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,080 control chromosomes in the GnomAD database, including 21,705 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 0.50 (21705 hom., cov: 33)
• Consequence: DCK NM_000788.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 15 publications found

Genes affected

DCK (HGNC:2704): (deoxycytidine kinase) Deoxycytidine kinase (DCK) is required for the phosphorylation of several deoxyribonucleosides and their nucleoside analogs. Deficiency of DCK is associated with resistance to antiviral and anticancer chemotherapeutic agents. Conversely, increased deoxycytidine kinase activity is associated with increased activation of these compounds to cytotoxic nucleoside triphosphate derivatives. DCK is clinically important because of its relationship to drug resistance and sensitivity. [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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCK	NM_000788.3	c.757-1205C>T		intron_variant	Intron 6 of 6	ENST00000286648.10	NP_000779.1
DCK	XM_047449689.1	c.541-1205C>T		intron_variant	Intron 6 of 6		XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10	c.757-1205C>T		intron_variant	Intron 6 of 6	1	NM_000788.3	ENSP00000286648.5
DCK	ENST00000504952.1	c.757-476C>T		intron_variant	Intron 6 of 7	3		ENSP00000421508.1
DCK	ENST00000504730.5	c.*41-1205C>T		intron_variant	Intron 5 of 5	3		ENSP00000425578.1
DCK	ENST00000503359.5	n.*701-1205C>T		intron_variant	Intron 6 of 6	2		ENSP00000426389.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75801 AN: 151962 Hom.: 21711 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.498 AC: 75799 AN: 152080 Hom.: 21705 Cov.: 33 AF XY: 0.499 AC XY: 37064 AN XY: 74336

African (AFR) AF: 0.192 AC: 7952 AN: 41520

American (AMR) AF: 0.654 AC: 10009 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2550 AN: 3466

East Asian (EAS) AF: 0.753 AC: 3903 AN: 5180

South Asian (SAS) AF: 0.545 AC: 2624 AN: 4816

European-Finnish (FIN) AF: 0.526 AC: 5552 AN: 10550

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.610 AC: 41473 AN: 67936

Other (OTH) AF: 0.567 AC: 1198 AN: 2114

Alfa AF: 0.573 Hom.: 69361

Bravo AF: 0.497

Asia WGS AF: 0.588 AC: 2045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.0
DANN	Benign	0.78
PhyloP100		-0.026
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: rs4694362; hg19: chr4-71893864;