rs17168564

Positions:

• chr7-14971199-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001350707.2(DGKB):​c.-188+3497A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,092 control chromosomes in the GnomAD database, including 1,839 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 0.15 (1839 hom., cov: 32)
• Consequence: DGKB NM_001350707.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKB	NM_001350707.2	c.-188+3497A>G		intron_variant
DGKB	NM_001350711.2	c.-188+3497A>G		intron_variant
DGKB	NM_001350717.2	c.-188+3497A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKB	ENST00000437998.1	c.-188+3497A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22944 AN: 151974 Hom.: 1837 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.0871

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.0908

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.151 AC: 22967 AN: 152092 Hom.: 1839 Cov.: 32 AF XY: 0.150 AC XY: 11163 AN XY: 74356

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.0871

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.0908

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.155

Alfa AF: 0.134 Hom.: 1992

Bravo AF: 0.155

Asia WGS AF: 0.209 AC: 729 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17168564; hg19: chr7-15010824;