rs2148004

chr13-42123703-A-G

Variant summary

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

The NM_178009.5(DGKH):c.193-3760A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,198 control chromosomes in the GnomAD database, including 5,473 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 0.26 (5473 hom., cov: 33)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755

Genes affected

DGKH (HGNC:2854): (diacylglycerol kinase eta) This gene encodes a member of the diacylglycerol kinase (DGK) enzyme family. Members of this family are involved in regulating intracellular concentrations of diacylglycerol and phosphatidic acid. Variation in this gene has been associated with bipolar disorder. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2014]

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 (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKH	NM_178009.5	c.193-3760A>G		intron_variant		ENST00000337343.9
DGKH	NM_001204504.3	c.193-3760A>G		intron_variant
DGKH	NM_152910.6	c.193-3760A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKH	ENST00000337343.9	c.193-3760A>G		intron_variant		1	NM_178009.5	P1
DGKH	ENST00000261491.9	c.193-3760A>G		intron_variant		1
DGKH	ENST00000379274.6	c.193-3760A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40322 AN: 152080 Hom.: 5472 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.265 AC: 40331 AN: 152198 Hom.: 5473 Cov.: 33 AF XY: 0.261 AC XY: 19446 AN XY: 74424

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.283

Alfa AF: 0.282 Hom.: 6085

Bravo AF: 0.261

Asia WGS AF: 0.221 AC: 770 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	7.0
Dann	Benign	0.54

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: rs2148004; hg19: chr13-42697839;