dbSNP rs4957018: PDCD6:c.478-521G>A (chr5-313896-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_013232.4(PDCD6):c.478-521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 156,624 control chromosomes in the GnomAD database, including 34,706 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 ( 33899 hom., cov: 32)

Exomes 𝑓: 0.59 ( 807 hom. )

Consequence

PDCD6
NM_013232.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.878

Publications

8 publications found

Variant links:

Genes affected

PDCD6 (HGNC:8765): (programmed cell death 6) This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. Calcium binding is important for homodimerization and for conformational changes required for binding to other protein partners. This gene product participates in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death. In mice deficient for this gene product, however, apoptosis was not blocked suggesting this gene product is functionally redundant. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is also located on the short arm of chromosome 5. [provided by RefSeq, May 2012]

PDCD6 links:

PDCD6-AHRR (HGNC:54724): (PDCD6-AHRR readthrough (NMD candidate)) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PDCD6-AHRR links:

ENSG00000286001 (HGNC:):

ENSG00000286001 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD6	NM_013232.4 link	c.478-521G>A		intron_variant	Intron 5 of 5	ENST00000264933.9	NP_037364.1	O75340-1Q53FC3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDCD6	ENST00000264933.9 link	c.478-521G>A	intron_variant	Intron 5 of 5	1	NM_013232.4	ENSP00000264933.4	O75340-1
ENSG00000286001	ENST00000651543.1 link	n.*1997+46G>A	intron_variant	Intron 23 of 23			ENSP00000499215.1	A0A494C1T6
PDCD6-AHRR	ENST00000675395.1 link	n.208+9675G>A	intron_variant	Intron 3 of 13			ENSP00000502570.1	A0A6Q8PH81

Frequencies

GnomAD3 genomes

AF:

0.662

AC:

100584

AN:

151974

Hom.:

33868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.767

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.682

Gnomad OTH

AF:

0.649

GnomAD4 exome

AF:

0.586

AC:

2658

AN:

4532

Hom.:

807

Cov.:

AF XY:

0.596

AC XY:

1365

AN XY:

2290

show subpopulations

African (AFR)

AF:

0.609

AC:

AN:

American (AMR)

AF:

0.502

AC:

228

AN:

454

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

AN:

East Asian (EAS)

AF:

0.100

AC:

AN:

South Asian (SAS)

AF:

0.670

AC:

150

AN:

224

European-Finnish (FIN)

AF:

0.682

AC:

AN:

Middle Eastern (MID)

AF:

0.538

AC:

860

AN:

1598

European-Non Finnish (NFE)

AF:

0.661

AC:

1174

AN:

1776

Other (OTH)

AF:

0.568

AC:

159

AN:

280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.662

AC:

100677

AN:

152092

Hom.:

33899

Cov.:

AF XY:

0.659

AC XY:

48957

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.717

AC:

29764

AN:

41498

American (AMR)

AF:

0.577

AC:

8823

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

1987

AN:

3468

East Asian (EAS)

AF:

0.260

AC:

1339

AN:

5156

South Asian (SAS)

AF:

0.645

AC:

3114

AN:

4826

European-Finnish (FIN)

AF:

0.668

AC:

7066

AN:

10572

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.682

AC:

46368

AN:

67972

Other (OTH)

AF:

0.648

AC:

1367

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1694

3389

5083

6778

8472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.675

Hom.:

17676

Bravo

AF:

0.652

Asia WGS

AF:

0.456

AC:

1585

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.9

(source)

DANN

Benign

0.38

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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