rs7684954

Positions:

• chr4-71009520-A-G
• chr4-71009520-A-T

Variant summary

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

The NM_000788.3(DCK):​c.207+11338A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,122 control chromosomes in the GnomAD database, including 54,280 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 (54280 hom., cov: 31)
• Consequence: DCK NM_000788.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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=-0.92).
• 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/exons	MANE	Protein	UniProt
DCK	NM_000788.3	c.207+11338A>G		intron_variant		ENST00000286648.10	NP_000779.1
DCK	XM_047449689.1	c.-10+11338A>G		intron_variant			XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10	c.207+11338A>G		intron_variant		1	NM_000788.3	ENSP00000286648	P1

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122854 AN: 152004 Hom.: 54273 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.808 AC: 122878 AN: 152122 Hom.: 54280 Cov.: 31 AF XY: 0.813 AC XY: 60425 AN XY: 74368

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.962

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.967

Gnomad4 OTH AF: 0.853

Alfa AF: 0.945 Hom.: 110630

Bravo AF: 0.785

Asia WGS AF: 0.909 AC: 3160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.67

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: rs7684954; hg19: chr4-71875237;