7-14570989-C-T

Variant names:

• chr7-14570989-C-T
• rs6949687
• NM_001350709.2:c.1770+3223G>A

Variant summary

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

The NM_001350709.2(DGKB):​c.1770+3223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,882 control chromosomes in the GnomAD database, including 20,314 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 0.52 (20314 hom., cov: 31)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.1770+3223G>A		intron_variant	Intron 20 of 25	ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.1770+3223G>A		intron_variant	Intron 20 of 25	5	NM_001350709.2	ENSP00000384909.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78295 AN: 151766 Hom.: 20287 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.516 AC: 78372 AN: 151882 Hom.: 20314 Cov.: 31 AF XY: 0.521 AC XY: 38664 AN XY: 74224

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.498

Alfa AF: 0.363 Hom.: 913

Bravo AF: 0.518

Asia WGS AF: 0.576 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.38

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: rs6949687; hg19: chr7-14610614;