rs9639213

Positions:

• chr7-14701222-G-A
• chr7-14701222-G-T

Variant summary

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

The NM_001350709.2(DGKB):​c.516+459C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,972 control chromosomes in the GnomAD database, including 14,382 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 0.40 (14382 hom., cov: 32)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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]

DGKB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.516+459C>T		intron_variant		ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.516+459C>T		intron_variant		5	NM_001350709.2	ENSP00000384909.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60434 AN: 151854 Hom.: 14379 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.398 AC: 60450 AN: 151972 Hom.: 14382 Cov.: 32 AF XY: 0.404 AC XY: 29994 AN XY: 74222

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.402

Alfa AF: 0.419 Hom.: 3958

Bravo AF: 0.395

Asia WGS AF: 0.664 AC: 2297 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
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: rs9639213; hg19: chr7-14740847;