rs198426

Positions:

• chr11-61723014-C-T

Variant summary

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

The ENST00000257215.10(DAGLA):​c.409+54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,378,648 control chromosomes in the GnomAD database, including 67,289 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 0.24 (5456 hom., cov: 33)
  • Exomes 𝑓: 0.30 (61833 hom.)
• Consequence: DAGLA ENST00000257215.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

Genes affected

DAGLA (HGNC:1165): (diacylglycerol lipase alpha) This gene encodes a diacylglycerol lipase. The encoded enzyme is involved in the biosynthesis of the endocannabinoid 2-arachidonoyl-glycerol.[provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAGLA	NM_006133.3	c.409+54C>T		intron_variant		ENST00000257215.10	NP_006124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAGLA	ENST00000257215.10	c.409+54C>T		intron_variant		1	NM_006133.3	ENSP00000257215	P1
DAGLA	ENST00000540717.1	c.386+54C>T		intron_variant, NMD_transcript_variant		5		ENSP00000440264

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35792 AN: 152066 Hom.: 5456 Cov.: 33

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.263

GnomAD4 exome AF: 0.304 AC: 373292 AN: 1226466 Hom.: 61833 AF XY: 0.303 AC XY: 188263 AN XY: 622010

Gnomad4 AFR exome AF: 0.0536

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.0301

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.235 AC: 35783 AN: 152182 Hom.: 5456 Cov.: 33 AF XY: 0.233 AC XY: 17329 AN XY: 74402

Gnomad4 AFR AF: 0.0595

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.0322

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.260

Alfa AF: 0.328 Hom.: 5026

Bravo AF: 0.226

Asia WGS AF: 0.106 AC: 370 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.017
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs198426; hg19: chr11-61490486;