4-168928238-C-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001166108.2(PALLD):​c.*2058C>G variant causes a 3 prime UTR 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
NM_001166108.2 3_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 3.32
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons MANE Protein UniProt
PALLDNM_001166108.2 linkuse as main transcriptc.*2058C>G 3_prime_UTR_variant 22/22 ENST00000505667.6 NP_001159580.1 Q8WX93-9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PALLDENST00000505667.6 linkuse as main transcriptc.*2058C>G 3_prime_UTR_variant 22/221 NM_001166108.2 ENSP00000425556.1 Q8WX93-9

Frequencies

GnomAD3 genomes
AF:
0.530
AC:
80446
AN:
151862
Hom.:
24909
Cov.:
31
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.:
0
AF XY:
0.666
AC XY:
9782
AN XY:
14684
show subpopulations
Gnomad4 AFR exome
AF:
0.200
Gnomad4 AMR exome
AF:
0.649
Gnomad4 ASJ exome
AF:
0.626
Gnomad4 EAS exome
AF:
0.875
Gnomad4 SAS exome
AF:
0.722
Gnomad4 FIN exome
AF:
0.718
Gnomad4 NFE exome
AF:
0.634
Gnomad4 OTH exome
AF:
0.597
GnomAD4 genome
AF:
0.529
AC:
80470
AN:
151980
Hom.:
24922
Cov.:
31
AF XY:
0.540
AC XY:
40122
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.188
Gnomad4 AMR
AF:
0.616
Gnomad4 ASJ
AF:
0.611
Gnomad4 EAS
AF:
0.884
Gnomad4 SAS
AF:
0.697
Gnomad4 FIN
AF:
0.732
Gnomad4 NFE
AF:
0.642
Gnomad4 OTH
AF:
0.551
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
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Pancreatic cancer, susceptibility to, 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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
17
DANN
Benign
0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1071738; hg19: chr4-169849389; API