4-168878239-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The ENST00000507735.6(PALLD):c.348G>A(p.Pro116Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000742 in 1,348,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.4e-7 ( 0 hom. )
Consequence
PALLD
ENST00000507735.6 synonymous
ENST00000507735.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.686
Publications
0 publications found
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]
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]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 4-168878239-G-A is Benign according to our data. Variant chr4-168878239-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 219949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.686 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000507735.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PALLD | NM_001166108.2 | MANE Select | c.1965-12683G>A | intron | N/A | NP_001159580.1 | |||
| PALLD | NM_001166110.2 | c.348G>A | p.Pro116Pro | synonymous | Exon 2 of 12 | NP_001159582.1 | |||
| PALLD | NM_016081.4 | c.1965-12683G>A | intron | N/A | NP_057165.3 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PALLD | ENST00000507735.6 | TSL:1 | c.348G>A | p.Pro116Pro | synonymous | Exon 2 of 12 | ENSP00000424016.1 | ||
| PALLD | ENST00000505667.6 | TSL:1 MANE Select | c.1965-12683G>A | intron | N/A | ENSP00000425556.1 | |||
| PALLD | ENST00000261509.10 | TSL:1 | c.1965-12683G>A | intron | N/A | ENSP00000261509.6 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.42e-7 AC: 1AN: 1348378Hom.: 0 Cov.: 46 AF XY: 0.00000150 AC XY: 1AN XY: 665546 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1348378
Hom.:
Cov.:
46
AF XY:
AC XY:
1
AN XY:
665546
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
28332
American (AMR)
AF:
AC:
0
AN:
33616
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23670
East Asian (EAS)
AF:
AC:
1
AN:
32272
South Asian (SAS)
AF:
AC:
0
AN:
76886
European-Finnish (FIN)
AF:
AC:
0
AN:
32684
Middle Eastern (MID)
AF:
AC:
0
AN:
4204
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1061112
Other (OTH)
AF:
AC:
0
AN:
55602
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)
-
-
1
Pancreatic adenocarcinoma (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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