rs1358445

Variant names:

• chr7-137521281-C-G
• rs1358445
• NM_001321708.2:c.2248+585G>C

Variant summary

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

The NM_001321708.2(DGKI):​c.2248+585G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 151,996 control chromosomes in the GnomAD database, including 1,394 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 0.092 (1394 hom., cov: 32)
• Consequence: DGKI NM_001321708.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321708.2. 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
	DGKI	NM_001321708.2	MANE Select	c.2248+585G>C		intron	N/A	NP_001308637.1
	DGKI	NM_001388092.1		c.2311+585G>C		intron	N/A	NP_001375021.1
	DGKI	NM_004717.3		c.2248+585G>C		intron	N/A	NP_004708.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKI	ENST00000614521.2	TSL:5 MANE Select	c.2248+585G>C		intron	N/A	ENSP00000479053.2
	DGKI	ENST00000453654.6	TSL:1	c.1348+585G>C		intron	N/A	ENSP00000392161.1
	DGKI	ENST00000424189.6	TSL:5	c.2311+585G>C		intron	N/A	ENSP00000396078.2

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 13986 AN: 151878 Hom.: 1395 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.00924

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.00529

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0848

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

GnomAD4 genome AF: 0.0921 AC: 14000 AN: 151996 Hom.: 1394 Cov.: 32 AF XY: 0.0927 AC XY: 6885 AN XY: 74288

African (AFR) AF: 0.240 AC: 9940 AN: 41450

American (AMR) AF: 0.117 AC: 1777 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00924 AC: 32 AN: 3464

East Asian (EAS) AF: 0.134 AC: 694 AN: 5162

South Asian (SAS) AF: 0.111 AC: 534 AN: 4816

European-Finnish (FIN) AF: 0.00529 AC: 56 AN: 10596

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 751 AN: 67956

Other (OTH) AF: 0.0844 AC: 178 AN: 2110

Alfa AF: 0.0547 Hom.: 110

Bravo AF: 0.108

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.61
PhyloP100		0.0060
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: rs1358445; hg19: chr7-137206027;