rs17167930

Positions:

• chr7-14148306-T-C

Variant summary

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

The NM_001350709.2(DGKB):​c.*825A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,520 control chromosomes in the GnomAD database, including 3,220 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 0.19 (3214 hom., cov: 33)
  • Exomes 𝑓: 0.18 (6 hom.)
• Consequence: DGKB NM_001350709.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

Genes affected

DGKB (HGNC:2850): (diacylglycerol kinase beta) Diacylglycerol kinases (DGKs) are regulators of the intracellular concentration of the second messenger diacylglycerol (DAG) and thus play a key role in cellular processes. Nine mammalian isotypes have been identified, which are encoded by separate genes. Mammalian DGK isozymes contain a conserved catalytic (kinase) domain and a cysteine-rich domain (CRD). The protein encoded by this gene is a diacylglycerol kinase, beta isotype. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKB	NM_001350709.2	c.*825A>G		3_prime_UTR_variant	26/26	ENST00000402815.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKB	ENST00000402815.6	c.*825A>G		3_prime_UTR_variant	26/26	5	NM_001350709.2	P4
DGKB	ENST00000399322.7	c.*825A>G		3_prime_UTR_variant	25/25	5		A1
DGKB	ENST00000403951.6	c.*825A>G		3_prime_UTR_variant	26/26	5		A1
DGKB	ENST00000407950.5			downstream_gene_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28692 AN: 151968 Hom.: 3203 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.177 AC: 77 AN: 434 Hom.: 6 Cov.: 0 AF XY: 0.192 AC XY: 50 AN XY: 260

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.189 AC: 28743 AN: 152086 Hom.: 3214 Cov.: 33 AF XY: 0.188 AC XY: 13943 AN XY: 74358

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.0993

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.197

Alfa AF: 0.141 Hom.: 2438

Bravo AF: 0.202

Asia WGS AF: 0.150 AC: 522 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	4.0
DANN	Benign	0.79

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: rs17167930; hg19: chr7-14187931;