7-14523420-C-T

Variant names:

• chr7-14523420-C-T
• rs1367781
• NM_001350709.2:c.1771-45195G>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.1771-45195G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,876 control chromosomes in the GnomAD database, including 12,276 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 0.40 (12276 hom., cov: 32)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 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.1771-45195G>A		intron	N/A	NP_001337638.1
	DGKB	NM_001350705.1		c.1774-45195G>A		intron	N/A	NP_001337634.1
	DGKB	NM_001350706.2		c.1774-45195G>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.1771-45195G>A		intron	N/A	ENSP00000384909.1
	DGKB	ENST00000406247.7	TSL:1	c.1774-45195G>A		intron	N/A	ENSP00000386066.3
	DGKB	ENST00000399322.7	TSL:5	c.1774-45195G>A		intron	N/A	ENSP00000382260.3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60214 AN: 151760 Hom.: 12253 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.397 AC: 60281 AN: 151876 Hom.: 12276 Cov.: 32 AF XY: 0.398 AC XY: 29533 AN XY: 74244

African (AFR) AF: 0.408 AC: 16892 AN: 41430

American (AMR) AF: 0.488 AC: 7432 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1412 AN: 3464

East Asian (EAS) AF: 0.391 AC: 2005 AN: 5134

South Asian (SAS) AF: 0.442 AC: 2125 AN: 4812

European-Finnish (FIN) AF: 0.369 AC: 3896 AN: 10550

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25262 AN: 67954

Other (OTH) AF: 0.390 AC: 825 AN: 2114

Alfa AF: 0.371 Hom.: 13342

Bravo AF: 0.409

Asia WGS AF: 0.482 AC: 1676 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.062
DANN	Benign	0.51
PhyloP100		-2.5
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: rs1367781; hg19: chr7-14563045;