Genetic Variant NM_004939.3:c.-60A>G (chr2-15591874-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004939.3(DDX1):c.-60A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,460,938 control chromosomes in the GnomAD database, including 296,658 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 0.69 ( 37431 hom., cov: 34)

Exomes 𝑓: 0.63 ( 259227 hom. )

Consequence

DDX1
NM_004939.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.154

Publications

11 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:

ENSG00000302930 (HGNC:):

ENSG00000302930 links:

Genome browser will be placed here

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=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX1	NM_004939.3 link	c.-60A>G		5_prime_UTR_variant	Exon 1 of 26	ENST00000233084.8	NP_004930.1	Q92499-1A3RJH1
LOC124905975	XR_007086224.1 link	n.-105T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX1	ENST00000233084.8 link	c.-60A>G		5_prime_UTR_variant	Exon 1 of 26	1	NM_004939.3	ENSP00000233084.3		Q92499-1

Frequencies

GnomAD3 genomes

AF:

0.691

AC:

105014

AN:

152008

Hom.:

37389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.857

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.684

Gnomad ASJ

AF:

0.592

Gnomad EAS

AF:

0.885

Gnomad SAS

AF:

0.760

Gnomad FIN

AF:

0.542

Gnomad MID

AF:

0.634

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.657

GnomAD4 exome

AF:

0.625

AC:

818064

AN:

1308812

Hom.:

259227

Cov.:

AF XY:

0.628

AC XY:

403858

AN XY:

643114

show subpopulations

African (AFR)

AF:

0.863

AC:

22257

AN:

25804

American (AMR)

AF:

0.679

AC:

15536

AN:

22884

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

12512

AN:

21382

East Asian (EAS)

AF:

0.927

AC:

26111

AN:

28176

South Asian (SAS)

AF:

0.731

AC:

50672

AN:

69302

European-Finnish (FIN)

AF:

0.537

AC:

25268

AN:

47014

Middle Eastern (MID)

AF:

0.575

AC:

2952

AN:

5136

European-Non Finnish (NFE)

AF:

0.606

AC:

627844

AN:

1035424

Other (OTH)

AF:

0.650

AC:

34912

AN:

53690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

14817

29634

44451

59268

74085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17734

35468

53202

70936

88670

<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:

0.691

AC:

105114

AN:

152126

Hom.:

37431

Cov.:

AF XY:

0.690

AC XY:

51343

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.857

AC:

35609

AN:

41546

American (AMR)

AF:

0.684

AC:

10457

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.592

AC:

2053

AN:

3470

East Asian (EAS)

AF:

0.886

AC:

4548

AN:

5136

South Asian (SAS)

AF:

0.760

AC:

3663

AN:

4820

European-Finnish (FIN)

AF:

0.542

AC:

5747

AN:

10596

Middle Eastern (MID)

AF:

0.606

AC:

177

AN:

292

European-Non Finnish (NFE)

AF:

0.602

AC:

40911

AN:

67958

Other (OTH)

AF:

0.657

AC:

1386

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1657

3314

4972

6629

8286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.550

Hom.:

1837

Bravo

AF:

0.708

Asia WGS

AF:

0.837

AC:

2908

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

8.6

(source)

DANN

Benign

0.61

PhyloP100

0.15

PromoterAI

0.080

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

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