rs4822466

chr22-23970015-G-A

Variant summary

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

The NM_001084393.2(DDTL):c.285-1271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 266,120 control chromosomes in the GnomAD database, including 33,568 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 0.44 (16961 hom., cov: 32)
  • Exomes 𝑓: 0.53 (16607 hom.)
• Consequence: DDTL NM_001084393.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

Genes affected

DDTL (HGNC:33446): (D-dopachrome tautomerase like) Predicted to enable lyase activity. Located in extracellular exosome. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDTL	NM_001084393.2	c.285-1271G>A		intron_variant		ENST00000215770.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDTL	ENST00000215770.6	c.285-1271G>A		intron_variant		2	NM_001084393.2	P1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66360 AN: 151886 Hom.: 16949 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.528 AC: 60241 AN: 114116 Hom.: 16607 AF XY: 0.526 AC XY: 28794 AN XY: 54734

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.464

Gnomad4 SAS exome AF: 0.574

Gnomad4 FIN exome AF: 0.597

Gnomad4 NFE exome AF: 0.538

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.437 AC: 66375 AN: 152004 Hom.: 16961 Cov.: 32 AF XY: 0.446 AC XY: 33109 AN XY: 74274

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.443

Alfa AF: 0.471 Hom.: 2737

Bravo AF: 0.415

Asia WGS AF: 0.524 AC: 1822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.1
Dann	Benign	0.38

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: rs4822466; hg19: chr22-24312204; COSMIC: COSV53159520; COSMIC: COSV53159520;