4-168542983-C-T

Variant names:

• chr4-168542983-C-T
• rs6836618
• NM_001166108.2:c.908+30571C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001166108.2(PALLD):​c.908+30571C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 151,256 control chromosomes in the GnomAD database, including 30,659 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 0.63 (30659 hom., cov: 27)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 2 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]

PALLD Gene-Disease associations (from GenCC):

• pancreatic cancer, susceptibility to, 1

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

LOC124900807 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166108.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	NM_001166108.2	MANE Select	c.908+30571C>T		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.908+30571C>T		intron	N/A	NP_057165.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.908+30571C>T		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.908+30571C>T		intron	N/A	ENSP00000261509.6	Q8WX93-2
	PALLD	ENST00000968439.1		c.908+30571C>T		intron	N/A	ENSP00000638498.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 95831 AN: 151140 Hom.: 30621 Cov.: 27

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.618

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.634 AC: 95915 AN: 151256 Hom.: 30659 Cov.: 27 AF XY: 0.641 AC XY: 47379 AN XY: 73900

African (AFR) AF: 0.616 AC: 25288 AN: 41046

American (AMR) AF: 0.668 AC: 10158 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1948 AN: 3462

East Asian (EAS) AF: 0.852 AC: 4369 AN: 5128

South Asian (SAS) AF: 0.683 AC: 3280 AN: 4800

European-Finnish (FIN) AF: 0.725 AC: 7590 AN: 10476

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.606 AC: 41107 AN: 67830

Other (OTH) AF: 0.623 AC: 1311 AN: 2104

Alfa AF: 0.614 Hom.: 64801

Bravo AF: 0.628

Asia WGS AF: 0.750 AC: 2605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.65
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6836618; hg19: chr4-169464134;