Genetic Variant NM_019070.5:c.853-78G>T (chr19-18924545-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019070.5(DDX49):c.853-78G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,498,574 control chromosomes in the GnomAD database, including 148,948 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 ( 12319 hom., cov: 32)

Exomes 𝑓: 0.44 ( 136629 hom. )

Consequence

DDX49
NM_019070.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.191

Publications

7 publications found

Variant links:

Genes affected

DDX49 (HGNC:18684): (DEAD-box helicase 49) Enables RNA binding activity. Involved in positive regulation of cell growth and regulation of rRNA stability. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DDX49 links:

ENSG00000268193 (HGNC:):

ENSG00000268193 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DDX49	NM_019070.5 link	c.853-78G>T	intron_variant	Intron 7 of 12	ENST00000247003.9	NP_061943.2	Q9Y6V7-1
DDX49	NR_033677.2 link	n.809-78G>T	intron_variant	Intron 7 of 12
DDX49	XM_011528084.4 link	c.532-78G>T	intron_variant	Intron 8 of 13		XP_011526386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX49	ENST00000247003.9 link	c.853-78G>T		intron_variant	Intron 7 of 12	1	NM_019070.5	ENSP00000247003.3		Q9Y6V7-1
ENSG00000268193	ENST00000596918.5 link	n.*167+6780C>A		intron_variant	Intron 4 of 6	5		ENSP00000469669.1		M0R1B8

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

55955

AN:

151752

Hom.:

12313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.533

Gnomad ASJ

AF:

0.603

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.590

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.437

GnomAD4 exome

AF:

0.443

AC:

596386

AN:

1346704

Hom.:

136629

AF XY:

0.440

AC XY:

297505

AN XY:

675984

show subpopulations

African (AFR)

AF:

0.120

AC:

3654

AN:

30576

American (AMR)

AF:

0.567

AC:

25062

AN:

44172

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

15460

AN:

25362

East Asian (EAS)

AF:

0.296

AC:

11575

AN:

39104

South Asian (SAS)

AF:

0.296

AC:

24789

AN:

83694

European-Finnish (FIN)

AF:

0.424

AC:

22162

AN:

52222

Middle Eastern (MID)

AF:

0.563

AC:

3135

AN:

5570

European-Non Finnish (NFE)

AF:

0.462

AC:

466386

AN:

1009354

Other (OTH)

AF:

0.427

AC:

24163

AN:

56650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

17477

34954

52432

69909

87386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13218

26436

39654

52872

66090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.369

AC:

55965

AN:

151870

Hom.:

12319

Cov.:

AF XY:

0.369

AC XY:

27370

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.127

AC:

5260

AN:

41482

American (AMR)

AF:

0.533

AC:

8136

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.603

AC:

2091

AN:

3468

East Asian (EAS)

AF:

0.286

AC:

1471

AN:

5152

South Asian (SAS)

AF:

0.291

AC:

1402

AN:

4812

European-Finnish (FIN)

AF:

0.424

AC:

4448

AN:

10490

Middle Eastern (MID)

AF:

0.579

AC:

168

AN:

290

European-Non Finnish (NFE)

AF:

0.465

AC:

31596

AN:

67900

Other (OTH)

AF:

0.433

AC:

916

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1649

3298

4947

6596

8245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.427

Hom.:

3039

Bravo

AF:

0.372

Asia WGS

AF:

0.273

AC:

950

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

(source)

DANN

Benign

0.67

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over