4-70996957-T-C

Variant names:

• chr4-70996957-T-C
• rs3775289
• NM_000788.3:c.92-1110T>C

Variant summary

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

The NM_000788.3(DCK):​c.92-1110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,182 control chromosomes in the GnomAD database, including 54,348 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 0.81 (54348 hom., cov: 32)
• Consequence: DCK NM_000788.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCK	NM_000788.3	c.92-1110T>C		intron_variant	Intron 1 of 6	ENST00000286648.10	NP_000779.1
DCK	XM_047449689.1	c.-125-1110T>C		intron_variant	Intron 1 of 6		XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10	c.92-1110T>C		intron_variant	Intron 1 of 6	1	NM_000788.3	ENSP00000286648.5

Frequencies

GnomAD3 genomes AF: 0.809 AC: 123057 AN: 152064 Hom.: 54342 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.809 AC: 123080 AN: 152182 Hom.: 54348 Cov.: 32 AF XY: 0.813 AC XY: 60537 AN XY: 74426

African (AFR) AF: 0.413 AC: 17129 AN: 41436

American (AMR) AF: 0.917 AC: 14039 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 3339 AN: 3472

East Asian (EAS) AF: 0.953 AC: 4937 AN: 5180

South Asian (SAS) AF: 0.949 AC: 4585 AN: 4832

European-Finnish (FIN) AF: 0.972 AC: 10312 AN: 10612

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.967 AC: 65808 AN: 68030

Other (OTH) AF: 0.855 AC: 1805 AN: 2112

Alfa AF: 0.902 Hom.: 114016

Bravo AF: 0.787

Asia WGS AF: 0.908 AC: 3158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.5
DANN	Benign	0.76
PhyloP100		0.88
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: rs3775289; hg19: chr4-71862674;