chr19-17315692-T-G

Variant names:

• chr19-17315692-T-G
• rs3826700
• NM_024050.6:c.137-242T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024050.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDA1	NM_024050.6	MANE Select	c.137-242T>G		intron	N/A	NP_076955.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDA1	ENST00000359866.9	TSL:1 MANE Select	c.137-242T>G		intron	N/A	ENSP00000352928.3
	DDA1	ENST00000593466.5	TSL:3	n.137-242T>G		intron	N/A	ENSP00000473086.1
	DDA1	ENST00000596582.1	TSL:3	n.137-242T>G		intron	N/A	ENSP00000472171.1

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

African (AFR) AF: 0.270 AC: 3361 AN: 12442

American (AMR) AF: 0.350 AC: 6701 AN: 19130

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 5324 AN: 12844

East Asian (EAS) AF: 0.0929 AC: 2844 AN: 30612

South Asian (SAS) AF: 0.429 AC: 19992 AN: 46650

European-Finnish (FIN) AF: 0.405 AC: 11557 AN: 28508

Middle Eastern (MID) AF: 0.383 AC: 691 AN: 1806

European-Non Finnish (NFE) AF: 0.435 AC: 112595 AN: 258778

Other (OTH) AF: 0.397 AC: 9757 AN: 24570

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

African (AFR) AF: 0.275 AC: 11397 AN: 41374

American (AMR) AF: 0.360 AC: 5486 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1469 AN: 3472

East Asian (EAS) AF: 0.121 AC: 621 AN: 5152

South Asian (SAS) AF: 0.432 AC: 2081 AN: 4812

European-Finnish (FIN) AF: 0.399 AC: 4200 AN: 10536

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.438 AC: 29768 AN: 67898

Other (OTH) AF: 0.378 AC: 796 AN: 2104

Alfa AF: 0.413 Hom.: 35392

Bravo AF: 0.360

Asia WGS AF: 0.304 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.43
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3826700; hg19: chr19-17426501;