rs834067

Positions:

• chr7-137536546-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321708.2(DGKI):​c.2148-14580T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,054 control chromosomes in the GnomAD database, including 6,411 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 0.22 (6411 hom., cov: 32)
• Consequence: DGKI NM_001321708.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

Genes affected

DGKI (HGNC:2855): (diacylglycerol kinase iota) This gene is a member of the type IV diacylglycerol kinase subfamily. Diacylglycerol kinases regulate the intracellular concentration of diacylglycerol through its phosphorylation, producing phosphatidic acid. The specific role of the enzyme encoded by this gene is undetermined, however, it may play a crucial role in the production of phosphatidic acid in the retina or in recessive forms of retinal degeneration. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKI	NM_001321708.2	c.2148-14580T>C		intron_variant		ENST00000614521.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKI	ENST00000614521.2	c.2148-14580T>C		intron_variant		5	NM_001321708.2	P3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33283 AN: 151936 Hom.: 6384 Cov.: 32

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.0594

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.219 AC: 33359 AN: 152054 Hom.: 6411 Cov.: 32 AF XY: 0.218 AC XY: 16206 AN XY: 74310

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.0995

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.0594

Gnomad4 NFE AF: 0.0827

Gnomad4 OTH AF: 0.192

Alfa AF: 0.121 Hom.: 1181

Bravo AF: 0.241

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs834067; hg19: chr7-137221292;