4-70993476-C-G

Variant names:

• chr4-70993476-C-G
• rs80143932
• ENST00000509617.1:c.-104-256C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509617.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCK	NM_000788.3	MANE Select	c.-360C>G		upstream_gene	N/A	NP_000779.1	F5CTF3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCK	ENST00000509617.1	TSL:3	c.-104-256C>G		intron	N/A	ENSP00000422971.1	D6R9C6
	MOB1B	ENST00000511449.1	TSL:3	n.429-4591C>G		intron	N/A
	DCK	ENST00000286648.10	TSL:1 MANE Select	c.-360C>G		upstream_gene	N/A	ENSP00000286648.5	P27707

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

African (AFR) AF: 0.0118 AC: 12 AN: 1020

American (AMR) AF: 0.0519 AC: 33 AN: 636

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 43 AN: 944

East Asian (EAS) AF: 0.158 AC: 243 AN: 1542

South Asian (SAS) AF: 0.0584 AC: 18 AN: 308

European-Finnish (FIN) AF: 0.00139 AC: 2 AN: 1436

Middle Eastern (MID) AF: 0.0309 AC: 5 AN: 162

European-Non Finnish (NFE) AF: 0.0151 AC: 256 AN: 16936

Other (OTH) AF: 0.0299 AC: 53 AN: 1774

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

African (AFR) AF: 0.0114 AC: 472 AN: 41574

American (AMR) AF: 0.0484 AC: 741 AN: 15308

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

East Asian (EAS) AF: 0.149 AC: 767 AN: 5136

South Asian (SAS) AF: 0.0446 AC: 215 AN: 4824

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0138 AC: 938 AN: 68008

Other (OTH) AF: 0.0331 AC: 70 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		-0.57
PromoterAI		-0.086	Neutral
Mutation Taster		=300/0	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: rs80143932; hg19: chr4-71859193;