rs38276

Positions:

• chr7-14265375-A-G
• chr7-14265375-A-T

Variant summary

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

The NM_001350709.2(DGKB):​c.2122+73140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.54 (22120 hom., cov: 18)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.2122+73140T>C		intron_variant		ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.2122+73140T>C		intron_variant		5	NM_001350709.2	ENSP00000384909	P4

Frequencies

GnomAD3 genomes AF: 0.544 AC: 73018 AN: 134132 Hom.: 22082 Cov.: 18

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.545 AC: 73091 AN: 134188 Hom.: 22120 Cov.: 18 AF XY: 0.550 AC XY: 35130 AN XY: 63866

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.542

Alfa AF: 0.413 Hom.: 5173

Bravo AF: 0.585

Asia WGS AF: 0.802 AC: 2784 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.36

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: rs38276; hg19: chr7-14305000; COSMIC: COSV51763250;