rs10499444

Variant names:

• chr7-14491106-C-G
• rs10499444
• NM_001350709.2:c.1771-12881G>C

Variant summary

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

The NM_001350709.2(DGKB):​c.1771-12881G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 152,066 control chromosomes in the GnomAD database, including 1,039 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 0.093 (1039 hom., cov: 31)
• Consequence: DGKB NM_001350709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 2 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 = 0.413 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.1771-12881G>C		intron	N/A	NP_001337638.1
	DGKB	NM_001350705.1		c.1774-12881G>C		intron	N/A	NP_001337634.1
	DGKB	NM_001350706.2		c.1774-12881G>C		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.1771-12881G>C		intron	N/A	ENSP00000384909.1
	DGKB	ENST00000406247.7	TSL:1	c.1774-12881G>C		intron	N/A	ENSP00000386066.3
	DGKB	ENST00000399322.7	TSL:5	c.1774-12881G>C		intron	N/A	ENSP00000382260.3

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14220 AN: 151948 Hom.: 1039 Cov.: 31

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.0869

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.0937

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0730

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0935 AC: 14217 AN: 152066 Hom.: 1039 Cov.: 31 AF XY: 0.101 AC XY: 7490 AN XY: 74306

African (AFR) AF: 0.0772 AC: 3206 AN: 41520

American (AMR) AF: 0.0689 AC: 1052 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 301 AN: 3464

East Asian (EAS) AF: 0.428 AC: 2202 AN: 5146

South Asian (SAS) AF: 0.0936 AC: 451 AN: 4820

European-Finnish (FIN) AF: 0.162 AC: 1710 AN: 10568

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4965 AN: 67964

Other (OTH) AF: 0.0842 AC: 178 AN: 2114

Alfa AF: 0.0876 Hom.: 85

Bravo AF: 0.0894

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.15
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: rs10499444; hg19: chr7-14530731;