rs196751

Variant names:

• chr7-14437482-T-C
• rs196751
• NM_001350709.2:c.1835+40679A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350709.2(DGKB):​c.1835+40679A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,748 control chromosomes in the GnomAD database, including 15,858 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 0.45 (15858 hom., cov: 31)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 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.1835+40679A>G		intron	N/A	NP_001337638.1
	DGKB	NM_001350705.1		c.1838+40679A>G		intron	N/A	NP_001337634.1
	DGKB	NM_001350706.2		c.1838+40679A>G		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.1835+40679A>G		intron	N/A	ENSP00000384909.1
	DGKB	ENST00000406247.7	TSL:1	c.1838+40679A>G		intron	N/A	ENSP00000386066.3
	DGKB	ENST00000399322.7	TSL:5	c.1838+40679A>G		intron	N/A	ENSP00000382260.3

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67978 AN: 151630 Hom.: 15853 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.448 AC: 67999 AN: 151748 Hom.: 15858 Cov.: 31 AF XY: 0.443 AC XY: 32866 AN XY: 74150

African (AFR) AF: 0.329 AC: 13635 AN: 41404

American (AMR) AF: 0.410 AC: 6238 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1887 AN: 3472

East Asian (EAS) AF: 0.366 AC: 1885 AN: 5154

South Asian (SAS) AF: 0.451 AC: 2172 AN: 4816

European-Finnish (FIN) AF: 0.442 AC: 4650 AN: 10518

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35952 AN: 67870

Other (OTH) AF: 0.479 AC: 1008 AN: 2106

Alfa AF: 0.474 Hom.: 3104

Bravo AF: 0.439

Asia WGS AF: 0.336 AC: 1162 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.0
DANN	Benign	0.68
PhyloP100		1.4
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: rs196751; hg19: chr7-14477107;