rs4822466

Variant names:

• chr22-23970015-G-A
• rs4822466
• NM_001084393.2:c.285-1271G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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]

ENSG00000290199 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001084393.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDTL	NM_001084393.2	MANE Select	c.285-1271G>A		intron	N/A	NP_001077862.1	A6NHG4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDTL	ENST00000215770.6	TSL:2 MANE Select	c.285-1271G>A		intron	N/A	ENSP00000215770.5	A6NHG4
	DDTL	ENST00000897122.1		c.291-1271G>A		intron	N/A	ENSP00000567181.1
	ENSG00000290199	ENST00000703580.1		n.309+3753C>T		intron	N/A

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

African (AFR) AF: 0.116 AC: 254 AN: 2190

American (AMR) AF: 0.375 AC: 42 AN: 112

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 290 AN: 708

East Asian (EAS) AF: 0.464 AC: 222 AN: 478

South Asian (SAS) AF: 0.574 AC: 1227 AN: 2136

European-Finnish (FIN) AF: 0.597 AC: 271 AN: 454

Middle Eastern (MID) AF: 0.407 AC: 105 AN: 258

European-Non Finnish (NFE) AF: 0.538 AC: 55881 AN: 103898

Other (OTH) AF: 0.502 AC: 1949 AN: 3882

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

African (AFR) AF: 0.157 AC: 6515 AN: 41482

American (AMR) AF: 0.504 AC: 7699 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2376 AN: 5158

South Asian (SAS) AF: 0.589 AC: 2841 AN: 4822

European-Finnish (FIN) AF: 0.610 AC: 6426 AN: 10542

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37279 AN: 67950

Other (OTH) AF: 0.443 AC: 934 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.38
PhyloP100		0.032
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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