4-70993963-G-C

Variant names:

• chr4-70993963-G-C
• rs9997790
• NM_000788.3:c.91+37G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000788.3(DCK):​c.91+37G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,469,492 control chromosomes in the GnomAD database, including 253 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 0.014 (23 hom., cov: 32)
  • Exomes 𝑓: 0.017 (230 hom.)
• Consequence: DCK NM_000788.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 4 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=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0142 (2165/152340) while in subpopulation NFE AF = 0.0197 (1343/68022). AF 95% confidence interval is 0.0189. There are 23 homozygotes in GnomAd4. There are 1068 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCK	NM_000788.3	c.91+37G>C		intron_variant	Intron 1 of 6	ENST00000286648.10	NP_000779.1
DCK	XM_047449689.1	c.-180G>C		5_prime_UTR_variant	Exon 1 of 7		XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10	c.91+37G>C		intron_variant	Intron 1 of 6	1	NM_000788.3	ENSP00000286648.5

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2165 AN: 152224 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.00398

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00785

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0186

GnomAD2 exomes AF: 0.0147 AC: 3445 AN: 234998 AF XY: 0.0150

Gnomad AFR exome AF: 0.00369

Gnomad AMR exome AF: 0.00939

Gnomad ASJ exome AF: 0.0244

Gnomad EAS exome AF: 0.0000574

Gnomad FIN exome AF: 0.0214

Gnomad NFE exome AF: 0.0200

Gnomad OTH exome AF: 0.0184

GnomAD4 exome AF: 0.0166 AC: 21845 AN: 1317152 Hom.: 230 Cov.: 19 AF XY: 0.0164 AC XY: 10859 AN XY: 662174

African (AFR) AF: 0.00340 AC: 104 AN: 30570

American (AMR) AF: 0.0102 AC: 441 AN: 43368

Ashkenazi Jewish (ASJ) AF: 0.0209 AC: 523 AN: 25052

East Asian (EAS) AF: 0.0000773 AC: 3 AN: 38818

South Asian (SAS) AF: 0.00727 AC: 599 AN: 82398

European-Finnish (FIN) AF: 0.0209 AC: 1101 AN: 52604

Middle Eastern (MID) AF: 0.0444 AC: 244 AN: 5492

European-Non Finnish (NFE) AF: 0.0183 AC: 17949 AN: 983082

Other (OTH) AF: 0.0158 AC: 881 AN: 55768

GnomAD4 genome AF: 0.0142 AC: 2165 AN: 152340 Hom.: 23 Cov.: 32 AF XY: 0.0143 AC XY: 1068 AN XY: 74496

African (AFR) AF: 0.00397 AC: 165 AN: 41586

American (AMR) AF: 0.0142 AC: 217 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.00766 AC: 37 AN: 4832

European-Finnish (FIN) AF: 0.0205 AC: 218 AN: 10622

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0197 AC: 1343 AN: 68022

Other (OTH) AF: 0.0184 AC: 39 AN: 2116

Alfa AF: 0.0107 Hom.: 6

Bravo AF: 0.0137

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.3
DANN	Benign	0.72
PhyloP100		0.39
PromoterAI		-0.050	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs9997790; hg19: chr4-71859680;