rs1646366

Variant names:

• chr7-137541177-C-A
• rs1646366
• NM_001321708.2:c.2147+11192G>T

Variant summary

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

The NM_001321708.2(DGKI):​c.2147+11192G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 152,212 control chromosomes in the GnomAD database, including 348 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 0.043 (348 hom., cov: 32)
• Consequence: DGKI NM_001321708.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKI	NM_001321708.2	c.2147+11192G>T		intron_variant	Intron 20 of 32	ENST00000614521.2	NP_001308637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKI	ENST00000614521.2	c.2147+11192G>T		intron_variant	Intron 20 of 32	5	NM_001321708.2	ENSP00000479053.2

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6515 AN: 152094 Hom.: 348 Cov.: 32

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.00581

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.0487

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

GnomAD4 genome AF: 0.0428 AC: 6517 AN: 152212 Hom.: 348 Cov.: 32 AF XY: 0.0437 AC XY: 3255 AN XY: 74432

African (AFR) AF: 0.0998 AC: 4143 AN: 41528

American (AMR) AF: 0.0987 AC: 1508 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.107 AC: 552 AN: 5170

South Asian (SAS) AF: 0.00540 AC: 26 AN: 4818

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10606

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00226 AC: 154 AN: 68016

Other (OTH) AF: 0.0482 AC: 102 AN: 2116

Alfa AF: 0.0195 Hom.: 75

Bravo AF: 0.0553

Asia WGS AF: 0.0400 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.76
DANN	Benign	0.67
PhyloP100		-0.16
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: rs1646366; hg19: chr7-137225923;