rs4584047

Variant names:

• chr7-14219621-G-T
• rs4584047
• NM_001350709.2:c.2123-41470C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350709.2(DGKB):​c.2123-41470C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,606 control chromosomes in the GnomAD database, including 38,181 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 0.70 (38181 hom., cov: 32)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.2123-41470C>A		intron_variant	Intron 23 of 25	ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.2123-41470C>A		intron_variant	Intron 23 of 25	5	NM_001350709.2	ENSP00000384909.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105375 AN: 151488 Hom.: 38135 Cov.: 32

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.696 AC: 105469 AN: 151606 Hom.: 38181 Cov.: 32 AF XY: 0.695 AC XY: 51497 AN XY: 74072

African (AFR) AF: 0.911 AC: 37772 AN: 41480

American (AMR) AF: 0.698 AC: 10617 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2347 AN: 3466

East Asian (EAS) AF: 0.633 AC: 3252 AN: 5140

South Asian (SAS) AF: 0.549 AC: 2646 AN: 4822

European-Finnish (FIN) AF: 0.659 AC: 6956 AN: 10558

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.587 AC: 39694 AN: 67628

Other (OTH) AF: 0.682 AC: 1430 AN: 2096

Alfa AF: 0.617 Hom.: 25025

Bravo AF: 0.710

Asia WGS AF: 0.653 AC: 2267 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.20
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4584047; hg19: chr7-14259246;