chr4-70993635-C-T

Variant names:

• chr4-70993635-C-T
• rs2306744
• ENST00000503359.5:n.-201C>T

Variant summary

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

The ENST00000503359.5(DCK):​n.-201C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 480,874 control chromosomes in the GnomAD database, including 519 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 0.022 (111 hom., cov: 32)
  • Exomes 𝑓: 0.028 (408 hom.)
• Consequence: DCK ENST00000503359.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83
• Publications: 23 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]

MOB1B (HGNC:29801): (MOB kinase activator 1B) The protein encoded by this gene is similar to the yeast Mob1 protein. Yeast Mob1 binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000503359.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCK	NM_000788.3	MANE Select	c.-201C>T		upstream_gene	N/A	NP_000779.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCK	ENST00000503359.5	TSL:2	n.-201C>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000426389.1
	DCK	ENST00000503359.5	TSL:2	n.-201C>T		5_prime_UTR	Exon 1 of 7	ENSP00000426389.1
	DCK	ENST00000509617.1	TSL:3	c.-104-97C>T		intron	N/A	ENSP00000422971.1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3374 AN: 152068 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.0280 AC: 9217 AN: 328692 Hom.: 408 Cov.: 2 AF XY: 0.0285 AC XY: 4916 AN XY: 172556

African (AFR) AF: 0.0107 AC: 76 AN: 7128

American (AMR) AF: 0.0529 AC: 451 AN: 8526

Ashkenazi Jewish (ASJ) AF: 0.0368 AC: 385 AN: 10464

East Asian (EAS) AF: 0.151 AC: 3454 AN: 22840

South Asian (SAS) AF: 0.0450 AC: 1179 AN: 26172

European-Finnish (FIN) AF: 0.00422 AC: 110 AN: 26064

Middle Eastern (MID) AF: 0.0361 AC: 57 AN: 1578

European-Non Finnish (NFE) AF: 0.0142 AC: 2922 AN: 205960

Other (OTH) AF: 0.0292 AC: 583 AN: 19960

GnomAD4 genome AF: 0.0221 AC: 3370 AN: 152182 Hom.: 111 Cov.: 32 AF XY: 0.0234 AC XY: 1738 AN XY: 74388

African (AFR) AF: 0.0114 AC: 474 AN: 41570

American (AMR) AF: 0.0483 AC: 738 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3472

East Asian (EAS) AF: 0.148 AC: 762 AN: 5134

South Asian (SAS) AF: 0.0443 AC: 214 AN: 4826

European-Finnish (FIN) AF: 0.00236 AC: 25 AN: 10610

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0140 AC: 949 AN: 67970

Other (OTH) AF: 0.0336 AC: 71 AN: 2116

Alfa AF: 0.00272 Hom.: 0

Bravo AF: 0.0256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.063
DANN	Benign	0.91
PhyloP100		-4.8
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=280/20	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: rs2306744; hg19: chr4-71859352;