7-137518721-C-T

Variant names:

• chr7-137518721-C-T
• rs6467709
• NM_001321708.2:c.2248+3145G>A

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+3145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,868 control chromosomes in the GnomAD database, including 6,180 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 (6180 hom., cov: 32)
• Consequence: DGKI NM_001321708.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKI	NM_001321708.2	c.2248+3145G>A		intron_variant	Intron 21 of 32	ENST00000614521.2	NP_001308637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKI	ENST00000614521.2	c.2248+3145G>A		intron_variant	Intron 21 of 32	5	NM_001321708.2	ENSP00000479053.2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32810 AN: 151750 Hom.: 6160 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.216 AC: 32873 AN: 151868 Hom.: 6180 Cov.: 32 AF XY: 0.215 AC XY: 15965 AN XY: 74224

African (AFR) AF: 0.503 AC: 20818 AN: 41384

American (AMR) AF: 0.189 AC: 2878 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3468

East Asian (EAS) AF: 0.136 AC: 701 AN: 5156

South Asian (SAS) AF: 0.274 AC: 1318 AN: 4816

European-Finnish (FIN) AF: 0.0598 AC: 633 AN: 10590

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0824 AC: 5594 AN: 67926

Other (OTH) AF: 0.194 AC: 409 AN: 2108

Alfa AF: 0.106 Hom.: 852

Bravo AF: 0.238

Asia WGS AF: 0.178 AC: 617 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0060
DANN	Benign	0.40
PhyloP100		-1.0
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: rs6467709; hg19: chr7-137203467;