7-14666031-G-T

Variant names:

• chr7-14666031-G-T
• rs1464822
• NM_001350709.2:c.1134+6898C>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.1134+6898C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 151,854 control chromosomes in the GnomAD database, including 47,138 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 0.79 (47138 hom., cov: 31)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350709.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKB	NM_001350709.2	MANE Select	c.1134+6898C>A		intron	N/A	NP_001337638.1
	DGKB	NM_001350705.1		c.1134+6898C>A		intron	N/A	NP_001337634.1
	DGKB	NM_001350706.2		c.1134+6898C>A		intron	N/A	NP_001337635.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKB	ENST00000402815.6	TSL:5 MANE Select	c.1134+6898C>A		intron	N/A	ENSP00000384909.1
	DGKB	ENST00000406247.7	TSL:1	c.1134+6898C>A		intron	N/A	ENSP00000386066.3
	DGKB	ENST00000399322.7	TSL:5	c.1134+6898C>A		intron	N/A	ENSP00000382260.3

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119342 AN: 151736 Hom.: 47125 Cov.: 31

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.786 AC: 119398 AN: 151854 Hom.: 47138 Cov.: 31 AF XY: 0.787 AC XY: 58382 AN XY: 74210

African (AFR) AF: 0.721 AC: 29879 AN: 41442

American (AMR) AF: 0.837 AC: 12716 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2699 AN: 3460

East Asian (EAS) AF: 0.893 AC: 4585 AN: 5132

South Asian (SAS) AF: 0.737 AC: 3555 AN: 4822

European-Finnish (FIN) AF: 0.824 AC: 8703 AN: 10556

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54608 AN: 67928

Other (OTH) AF: 0.782 AC: 1651 AN: 2110

Alfa AF: 0.787 Hom.: 5853

Bravo AF: 0.788

Asia WGS AF: 0.794 AC: 2743 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.16
PhyloP100		-0.36
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: rs1464822; hg19: chr7-14705656; COSMIC: COSV51789764;