7-14933259-A-C

Position:

• chr7-14933259-A-C

Variant summary

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

The NM_001350707.2(DGKB):​c.-188+41437T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,146 control chromosomes in the GnomAD database, including 5,838 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 0.22 (5838 hom., cov: 32)
• Consequence: DGKB NM_001350707.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKB	NM_001350707.2	c.-188+41437T>G		intron_variant			NP_001337636.1
DGKB	NM_001350711.2	c.-188+41437T>G		intron_variant			NP_001337640.1
DGKB	NM_001350717.2	c.-188+41437T>G		intron_variant			NP_001337646.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000437998.1	c.-188+41437T>G		intron_variant		4		ENSP00000405569

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33447 AN: 152028 Hom.: 5815 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.0948

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.220 AC: 33494 AN: 152146 Hom.: 5838 Cov.: 32 AF XY: 0.230 AC XY: 17105 AN XY: 74384

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.0949

Gnomad4 OTH AF: 0.204

Alfa AF: 0.126 Hom.: 1627

Bravo AF: 0.228

Asia WGS AF: 0.630 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7787411; hg19: chr7-14972884;