chr7-14406292-T-C

Variant names:

• chr7-14406292-T-C
• rs6971925
• NM_001350709.2:c.1836-60901A>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.1836-60901A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 152,098 control chromosomes in the GnomAD database, including 72,444 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 0.98 (72444 hom., cov: 31)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 14 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKB	NM_001350709.2	MANE Select	c.1836-60901A>G		intron	N/A	NP_001337638.1	B5MBY2
	DGKB	NM_001350705.1		c.1839-60901A>G		intron	N/A	NP_001337634.1	Q9Y6T7-1
	DGKB	NM_001350706.2		c.1839-60901A>G		intron	N/A	NP_001337635.1	Q9Y6T7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKB	ENST00000402815.6	TSL:5 MANE Select	c.1836-60901A>G		intron	N/A	ENSP00000384909.1	B5MBY2
	DGKB	ENST00000406247.7	TSL:1	c.1839-60901A>G		intron	N/A	ENSP00000386066.3	Q9Y6T7-2
	DGKB	ENST00000399322.7	TSL:5	c.1839-60901A>G		intron	N/A	ENSP00000382260.3	Q9Y6T7-1

Frequencies

GnomAD3 genomes AF: 0.975 AC: 148239 AN: 151980 Hom.: 72395 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.971

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

GnomAD4 genome AF: 0.975 AC: 148348 AN: 152098 Hom.: 72444 Cov.: 31 AF XY: 0.974 AC XY: 72404 AN XY: 74340

African (AFR) AF: 0.964 AC: 40040 AN: 41528

American (AMR) AF: 0.909 AC: 13845 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3441 AN: 3470

East Asian (EAS) AF: 0.901 AC: 4639 AN: 5148

South Asian (SAS) AF: 0.970 AC: 4679 AN: 4826

European-Finnish (FIN) AF: 0.993 AC: 10531 AN: 10610

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67921 AN: 67966

Other (OTH) AF: 0.970 AC: 2049 AN: 2112

Alfa AF: 0.986 Hom.: 212741

Bravo AF: 0.969

Asia WGS AF: 0.927 AC: 3225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		-0.69
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: rs6971925; hg19: chr7-14445917;