7-14866213-C-T

Variant names:

• chr7-14866213-C-T
• rs7788248
• NM_001350709.2:c.-187-24763G>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.-187-24763G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,070 control chromosomes in the GnomAD database, including 2,960 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 0.19 (2960 hom., cov: 32)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.-187-24763G>A		intron_variant	Intron 1 of 25	ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.-187-24763G>A		intron_variant	Intron 1 of 25	5	NM_001350709.2	ENSP00000384909.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28602 AN: 151956 Hom.: 2966 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.188 AC: 28600 AN: 152070 Hom.: 2960 Cov.: 32 AF XY: 0.184 AC XY: 13702 AN XY: 74348

African (AFR) AF: 0.247 AC: 10250 AN: 41450

American (AMR) AF: 0.126 AC: 1926 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3472

East Asian (EAS) AF: 0.292 AC: 1504 AN: 5152

South Asian (SAS) AF: 0.270 AC: 1303 AN: 4818

European-Finnish (FIN) AF: 0.0780 AC: 827 AN: 10604

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10988 AN: 67992

Other (OTH) AF: 0.205 AC: 431 AN: 2104

Alfa AF: 0.178 Hom.: 7791

Bravo AF: 0.193

Asia WGS AF: 0.254 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.69
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7788248; hg19: chr7-14905838;