rs10499444

Positions:

• chr7-14491106-C-G

Variant summary

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

The NM_001350709.2(DGKB):​c.1771-12881G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 152,066 control chromosomes in the GnomAD database, including 1,039 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 0.093 (1039 hom., cov: 31)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKB	NM_001350709.2	c.1771-12881G>C		intron_variant		ENST00000402815.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKB	ENST00000402815.6	c.1771-12881G>C		intron_variant		5	NM_001350709.2	P4

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14220 AN: 151948 Hom.: 1039 Cov.: 31

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.0869

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.0937

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0730

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0935 AC: 14217 AN: 152066 Hom.: 1039 Cov.: 31 AF XY: 0.101 AC XY: 7490 AN XY: 74306

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.0689

Gnomad4 ASJ AF: 0.0869

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.0731

Gnomad4 OTH AF: 0.0842

Alfa AF: 0.0876 Hom.: 85

Bravo AF: 0.0894

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.57

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: rs10499444; hg19: chr7-14530731;