rs3826700

chr19-17315692-T-G

Variant summary

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

The NM_024050.6(DDA1):c.137-242T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 587,120 control chromosomes in the GnomAD database, including 47,245 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 0.37 (10976 hom., cov: 30)
  • Exomes 𝑓: 0.40 (36269 hom.)
• Consequence: DDA1 NM_024050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

Genes affected

DDA1 (HGNC:28360): (DET1 and DDB1 associated 1) Involved in protein polyubiquitination. Part of Cul4-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDA1	NM_024050.6	c.137-242T>G		intron_variant		ENST00000359866.9
DDA1	XR_007067003.1	n.229-242T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDA1	ENST00000359866.9	c.137-242T>G		intron_variant		1	NM_024050.6	P1
DDA1	ENST00000593466.5	c.137-242T>G		intron_variant, NMD_transcript_variant		3
DDA1	ENST00000596582.1	c.137-242T>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56292 AN: 151664 Hom.: 10958 Cov.: 30

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.397 AC: 172822 AN: 435340 Hom.: 36269 AF XY: 0.402 AC XY: 92989 AN XY: 231592

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.415

Gnomad4 EAS exome AF: 0.0929

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.435

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.371 AC: 56341 AN: 151780 Hom.: 10976 Cov.: 30 AF XY: 0.369 AC XY: 27332 AN XY: 74138

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.378

Alfa AF: 0.427 Hom.: 22426

Bravo AF: 0.360

Asia WGS AF: 0.304 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.6
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3826700; hg19: chr19-17426501;