4-168928238-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000507699.1(PALLD):n.3650C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 183,792 control chromosomes in the GnomAD database, including 32,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 24922 hom., cov: 31)

Exomes 𝑓: 0.66 ( 7246 hom. )

Consequence

PALLD
ENST00000507699.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.32

Publications

28 publications found

Variant links:

Genes affected

PALLD (HGNC:17068): (palladin, cytoskeletal associated protein) This gene encodes a cytoskeletal protein that is required for organizing the actin cytoskeleton. The protein is a component of actin-containing microfilaments, and it is involved in the control of cell shape, adhesion, and contraction. Polymorphisms in this gene are associated with a susceptibility to pancreatic cancer type 1, and also with a risk for myocardial infarction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

PALLD links:

CBR4 (HGNC:25891): (carbonyl reductase 4) Enables several functions, including 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; NADPH binding activity; and NADPH dehydrogenase (quinone) activity. Involved in fatty acid biosynthetic process; glycoside metabolic process; and protein tetramerization. Located in mitochondrial matrix. Part of oxidoreductase complex. [provided by Alliance of Genome Resources, Apr 2022]

CBR4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 4-168928238-C-G is Benign according to our data. Variant chr4-168928238-C-G is described in ClinVar as Benign. ClinVar VariationId is 348069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALLD	NM_001166108.2 link	c.*2058C>G		3_prime_UTR_variant	Exon 22 of 22	ENST00000505667.6	NP_001159580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6 link	c.*2058C>G		3_prime_UTR_variant	Exon 22 of 22	1	NM_001166108.2	ENSP00000425556.1

Frequencies

GnomAD3 genomes

AF:

0.530

AC:

80446

AN:

151862

Hom.:

24909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.884

Gnomad SAS

AF:

0.696

Gnomad FIN

AF:

0.732

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.546

GnomAD4 exome

AF:

0.663

AC:

21088

AN:

31812

Hom.:

7246

Cov.:

AF XY:

0.666

AC XY:

9782

AN XY:

14684

show subpopulations

African (AFR)

AF:

0.200

AC:

219

AN:

1096

American (AMR)

AF:

0.649

AC:

484

AN:

746

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

1278

AN:

2042

East Asian (EAS)

AF:

0.875

AC:

5322

AN:

6082

South Asian (SAS)

AF:

0.722

AC:

182

AN:

252

European-Finnish (FIN)

AF:

0.718

AC:

319

AN:

444

Middle Eastern (MID)

AF:

0.524

AC:

110

AN:

210

European-Non Finnish (NFE)

AF:

0.634

AC:

11621

AN:

18338

Other (OTH)

AF:

0.597

AC:

1553

AN:

2602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

328

655

983

1310

1638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.529

AC:

80470

AN:

151980

Hom.:

24922

Cov.:

AF XY:

0.540

AC XY:

40122

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.188

AC:

7786

AN:

41394

American (AMR)

AF:

0.616

AC:

9408

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

2115

AN:

3464

East Asian (EAS)

AF:

0.884

AC:

4572

AN:

5172

South Asian (SAS)

AF:

0.697

AC:

3361

AN:

4820

European-Finnish (FIN)

AF:

0.732

AC:

7730

AN:

10554

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.642

AC:

43629

AN:

67982

Other (OTH)

AF:

0.551

AC:

1161

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1585

3170

4754

6339

7924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.463

Hom.:

1575

Bravo

AF:

0.507

Asia WGS

AF:

0.767

AC:

2664

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pancreatic cancer, susceptibility to, 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

3.3

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over