dbSNP rs34104444: PDCD4:p.Gln173Gln (chr10-110885330-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014456.5(PDCD4):c.519G>A(p.Gln173Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 1,588,624 control chromosomes in the GnomAD database, including 1,863 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 0.058 ( 329 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1534 hom. )

Consequence

PDCD4
NM_014456.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.16

Publications

7 publications found

Variant links:

Genes affected

PDCD4 (HGNC:8763): (programmed cell death 4) This gene is a tumor suppressor and encodes a protein that binds to the eukaryotic translation initiation factor 4A1 and inhibits its function by preventing RNA binding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

PDCD4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP7

Synonymous conserved (PhyloP=3.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD4	NM_014456.5 link	c.519G>A	p.Gln173Gln	synonymous_variant	Exon 5 of 12	ENST00000280154.12	NP_055271.2	Q53EL6-1
PDCD4	NM_145341.4 link	c.486G>A	p.Gln162Gln	synonymous_variant	Exon 6 of 13		NP_663314.1	Q53EL6-2
PDCD4	NM_001199492.2 link	c.477G>A	p.Gln159Gln	synonymous_variant	Exon 5 of 12		NP_001186421.1	B4DKX4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD4	ENST00000280154.12 link	c.519G>A	p.Gln173Gln	synonymous_variant	Exon 5 of 12	1	NM_014456.5	ENSP00000280154.7		Q53EL6-1

Frequencies

GnomAD3 genomes

AF:

0.0579

AC:

8800

AN:

152032

Hom.:

330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0299

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00850

Gnomad FIN

AF:

0.0545

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0437

Gnomad OTH

AF:

0.0498

GnomAD2 exomes

AF:

0.0375

AC:

9162

AN:

244490

AF XY:

0.0359

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0231

Gnomad ASJ exome

AF:

0.0678

Gnomad EAS exome

AF:

0.000225

Gnomad FIN exome

AF:

0.0500

Gnomad NFE exome

AF:

0.0404

Gnomad OTH exome

AF:

0.0401

GnomAD4 exome

AF:

0.0426

AC:

61212

AN:

1436474

Hom.:

1534

Cov.:

AF XY:

0.0413

AC XY:

29554

AN XY:

715900

show subpopulations

African (AFR)

AF:

0.110

AC:

3547

AN:

32390

American (AMR)

AF:

0.0253

AC:

1102

AN:

43542

Ashkenazi Jewish (ASJ)

AF:

0.0672

AC:

1735

AN:

25826

East Asian (EAS)

AF:

0.0000770

AC:

AN:

38982

South Asian (SAS)

AF:

0.0113

AC:

963

AN:

84940

European-Finnish (FIN)

AF:

0.0477

AC:

2539

AN:

53246

Middle Eastern (MID)

AF:

0.0557

AC:

319

AN:

5722

European-Non Finnish (NFE)

AF:

0.0441

AC:

48177

AN:

1092356

Other (OTH)

AF:

0.0475

AC:

2827

AN:

59470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

2296

4592

6887

9183

11479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1850

3700

5550

7400

9250

<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:

0.0578

AC:

8801

AN:

152150

Hom.:

329

Cov.:

AF XY:

0.0562

AC XY:

4180

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.106

AC:

4393

AN:

41508

American (AMR)

AF:

0.0298

AC:

456

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0674

AC:

234

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00767

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0545

AC:

575

AN:

10560

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0437

AC:

2972

AN:

68012

Other (OTH)

AF:

0.0492

AC:

104

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

433

865

1298

1730

2163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0463

Hom.:

416

Bravo

AF:

0.0581

Asia WGS

AF:

0.0100

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.9

(source)

DANN

Benign

0.70

PhyloP100

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

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