rs6561030

Variant names:

• chr13-42057583-C-A
• rs6561030
• NM_178009.5:c.192+8618C>A

Variant summary

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

The NM_178009.5(DGKH):​c.192+8618C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,110 control chromosomes in the GnomAD database, including 2,524 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 0.18 (2524 hom., cov: 32)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 10 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKH	NM_178009.5	c.192+8618C>A		intron_variant	Intron 1 of 29	ENST00000337343.9	NP_821077.1
DGKH	NM_001204504.3	c.192+8618C>A		intron_variant	Intron 2 of 29		NP_001191433.1
DGKH	NM_152910.6	c.192+8618C>A		intron_variant	Intron 1 of 28		NP_690874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.192+8618C>A		intron_variant	Intron 1 of 29	1	NM_178009.5	ENSP00000337572.4
DGKH	ENST00000261491.9	c.192+8618C>A		intron_variant	Intron 1 of 28	1		ENSP00000261491.4
DGKH	ENST00000379274.6	c.192+8618C>A		intron_variant	Intron 2 of 29	2		ENSP00000368576.3
DGKH	ENST00000611224.1	c.145-8508C>A		intron_variant	Intron 1 of 1	2		ENSP00000482250.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26699 AN: 151990 Hom.: 2520 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.176 AC: 26719 AN: 152110 Hom.: 2524 Cov.: 32 AF XY: 0.178 AC XY: 13201 AN XY: 74366

African (AFR) AF: 0.218 AC: 9028 AN: 41494

American (AMR) AF: 0.126 AC: 1930 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3468

East Asian (EAS) AF: 0.320 AC: 1659 AN: 5178

South Asian (SAS) AF: 0.199 AC: 958 AN: 4818

European-Finnish (FIN) AF: 0.172 AC: 1812 AN: 10564

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10101 AN: 67990

Other (OTH) AF: 0.192 AC: 406 AN: 2116

Alfa AF: 0.159 Hom.: 7301

Bravo AF: 0.174

Asia WGS AF: 0.293 AC: 1017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.77
PhyloP100		1.2
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: rs6561030; hg19: chr13-42631719;