4-168913983-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001166108.2(PALLD):c.2679A>G(p.Arg893Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,611,468 control chromosomes in the GnomAD database, including 9,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1389 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7735 hom. )

Consequence

PALLD
NM_001166108.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.523

Publications

14 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 4-168913983-A-G is Benign according to our data. Variant chr4-168913983-A-G is described in ClinVar as Benign. ClinVar VariationId is 348043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.523 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALLD	NM_001166108.2 link	c.2679A>G	p.Arg893Arg	synonymous_variant	Exon 16 of 22	ENST00000505667.6	NP_001159580.1	Q8WX93-9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6 link	c.2679A>G	p.Arg893Arg	synonymous_variant	Exon 16 of 22	1	NM_001166108.2	ENSP00000425556.1		Q8WX93-9

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18837

AN:

152094

Hom.:

1386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.0387

Gnomad SAS

AF:

0.0531

Gnomad FIN

AF:

0.0445

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.125

GnomAD2 exomes

AF:

0.0916

AC:

23027

AN:

251416

AF XY:

0.0901

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0695

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.0342

Gnomad FIN exome

AF:

0.0454

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.0984

AC:

143631

AN:

1459256

Hom.:

7735

Cov.:

AF XY:

0.0971

AC XY:

70531

AN XY:

726090

show subpopulations

African (AFR)

AF:

0.202

AC:

6749

AN:

33400

American (AMR)

AF:

0.0729

AC:

3260

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

4787

AN:

26114

East Asian (EAS)

AF:

0.0420

AC:

1665

AN:

39676

South Asian (SAS)

AF:

0.0517

AC:

4456

AN:

86214

European-Finnish (FIN)

AF:

0.0503

AC:

2689

AN:

53412

Middle Eastern (MID)

AF:

0.147

AC:

845

AN:

5762

European-Non Finnish (NFE)

AF:

0.102

AC:

112720

AN:

1109660

Other (OTH)

AF:

0.107

AC:

6460

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6269

12538

18807

25076

31345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4178

8356

12534

16712

20890

<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:

0.124

AC:

18853

AN:

152212

Hom.:

1389

Cov.:

AF XY:

0.118

AC XY:

8821

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.198

AC:

8196

AN:

41484

American (AMR)

AF:

0.111

AC:

1702

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

648

AN:

3468

East Asian (EAS)

AF:

0.0387

AC:

201

AN:

5188

South Asian (SAS)

AF:

0.0533

AC:

257

AN:

4818

European-Finnish (FIN)

AF:

0.0445

AC:

473

AN:

10632

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

6982

AN:

68018

Other (OTH)

AF:

0.124

AC:

262

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

844

1688

2531

3375

4219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.114

Hom.:

808

Bravo

AF:

0.133

Asia WGS

AF:

0.0430

AC:

150

AN:

3476

EpiCase

AF:

0.114

EpiControl

AF:

0.112

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pancreatic cancer, susceptibility to, 1

Benign:2

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

- -

not specified

Benign:1

Jul 30, 2020

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Pancreatic adenocarcinoma

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.52

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