4-70993476-C-G

Position:

• chr4-70993476-C-G

Variant summary

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

The ENST00000509617.1(DCK):​c.-104-256C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 177,018 control chromosomes in the GnomAD database, including 147 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 (112 hom., cov: 32)
  • Exomes 𝑓: 0.027 (35 hom.)
• Consequence: DCK ENST00000509617.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000509617.1	c.-104-256C>G		intron_variant		3		ENSP00000422971.1
MOB1B	ENST00000511449.1	n.429-4591C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3368 AN: 152144 Hom.: 113 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0321

GnomAD4 exome AF: 0.0269 AC: 665 AN: 24758 Hom.: 35 Cov.: 0 AF XY: 0.0270 AC XY: 343 AN XY: 12714

Gnomad4 AFR exome AF: 0.0118

Gnomad4 AMR exome AF: 0.0519

Gnomad4 ASJ exome AF: 0.0456

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.0584

Gnomad4 FIN exome AF: 0.00139

Gnomad4 NFE exome AF: 0.0151

Gnomad4 OTH exome AF: 0.0299

GnomAD4 genome AF: 0.0221 AC: 3365 AN: 152260 Hom.: 112 Cov.: 32 AF XY: 0.0234 AC XY: 1740 AN XY: 74430

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0484

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.0446

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.00271 Hom.: 0

Bravo AF: 0.0256

Asia WGS AF: 0.0970 AC: 335 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	1.6
DANN	Benign	0.54

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: rs80143932; hg19: chr4-71859193;