dbSNP rs10929378: DDX1:p.Asn304Asn (chr2-15607269-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_004939.3(DDX1):c.912C>T(p.Asn304Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 1,609,522 control chromosomes in the GnomAD database, including 301,706 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 0.66 ( 34087 hom., cov: 32)

Exomes 𝑓: 0.60 ( 267619 hom. )

Consequence

DDX1
NM_004939.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.700

Publications

26 publications found

Variant links:

Genes affected

DDX1 (HGNC:2734): (DEAD-box helicase 1) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein that acts as an ATP-dependent RNA helicase that has been found to promote coronaviruses replication. [provided by RefSeq, Aug 2021]

DDX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=0.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX1	NM_004939.3 link	c.912C>T	p.Asn304Asn	synonymous_variant	Exon 13 of 26	ENST00000233084.8	NP_004930.1	Q92499-1A3RJH1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX1	ENST00000233084.8 link	c.912C>T	p.Asn304Asn	synonymous_variant	Exon 13 of 26	1	NM_004939.3	ENSP00000233084.3		Q92499-1

Frequencies

GnomAD3 genomes

AF:

0.659

AC:

100103

AN:

151886

Hom.:

34051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.611

Gnomad AMR

AF:

0.656

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.886

Gnomad SAS

AF:

0.747

Gnomad FIN

AF:

0.539

Gnomad MID

AF:

0.596

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.622

GnomAD2 exomes

AF:

0.640

AC:

160845

AN:

251326

AF XY:

0.634

show subpopulations

Gnomad AFR exome

AF:

0.817

Gnomad AMR exome

AF:

0.677

Gnomad ASJ exome

AF:

0.573

Gnomad EAS exome

AF:

0.886

Gnomad FIN exome

AF:

0.532

Gnomad NFE exome

AF:

0.570

Gnomad OTH exome

AF:

0.602

GnomAD4 exome

AF:

0.600

AC:

875049

AN:

1457518

Hom.:

267619

Cov.:

AF XY:

0.603

AC XY:

437527

AN XY:

725336

show subpopulations

African (AFR)

AF:

0.816

AC:

27260

AN:

33410

American (AMR)

AF:

0.669

AC:

29916

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

14931

AN:

26082

East Asian (EAS)

AF:

0.916

AC:

36313

AN:

39664

South Asian (SAS)

AF:

0.720

AC:

61990

AN:

86144

European-Finnish (FIN)

AF:

0.532

AC:

28383

AN:

53392

Middle Eastern (MID)

AF:

0.540

AC:

3111

AN:

5764

European-Non Finnish (NFE)

AF:

0.574

AC:

635770

AN:

1108088

Other (OTH)

AF:

0.620

AC:

37375

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

16988

33975

50963

67950

84938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17820

35640

53460

71280

89100

<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:

0.659

AC:

100201

AN:

152004

Hom.:

34087

Cov.:

AF XY:

0.660

AC XY:

49053

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.809

AC:

33563

AN:

41476

American (AMR)

AF:

0.657

AC:

10020

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2013

AN:

3466

East Asian (EAS)

AF:

0.887

AC:

4582

AN:

5168

South Asian (SAS)

AF:

0.747

AC:

3599

AN:

4818

European-Finnish (FIN)

AF:

0.539

AC:

5681

AN:

10532

Middle Eastern (MID)

AF:

0.562

AC:

164

AN:

292

European-Non Finnish (NFE)

AF:

0.569

AC:

38703

AN:

67966

Other (OTH)

AF:

0.624

AC:

1319

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1640

3280

4921

6561

8201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.606

Hom.:

15119

Bravo

AF:

0.673

Asia WGS

AF:

0.828

AC:

2879

AN:

3478

EpiCase

AF:

0.569

EpiControl

AF:

0.563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

6.8

(source)

DANN

Benign

0.65

PhyloP100

0.70

Mutation Taster

=98/2

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