rs1170195

Positions:

• chr13-42094549-A-G
• chr13-42094549-A-T

Variant summary

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

The NM_178009.5(DGKH):​c.193-32914A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,054 control chromosomes in the GnomAD database, including 12,575 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 0.40 (12575 hom., cov: 32)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKH	NM_178009.5	c.193-32914A>G		intron_variant		ENST00000337343.9	NP_821077.1
DGKH	NM_001204504.3	c.193-32914A>G		intron_variant			NP_001191433.1
DGKH	NM_152910.6	c.193-32914A>G		intron_variant			NP_690874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.193-32914A>G		intron_variant		1	NM_178009.5	ENSP00000337572	P1
DGKH	ENST00000261491.9	c.193-32914A>G		intron_variant		1		ENSP00000261491
DGKH	ENST00000379274.6	c.193-32914A>G		intron_variant		2		ENSP00000368576

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60233 AN: 151936 Hom.: 12552 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.397 AC: 60316 AN: 152054 Hom.: 12575 Cov.: 32 AF XY: 0.397 AC XY: 29497 AN XY: 74328

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.397

Alfa AF: 0.364 Hom.: 13425

Bravo AF: 0.411

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.27

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: rs1170195; hg19: chr13-42668685;