4-168843338-C-T

Variant names:

• chr4-168843338-C-T
• rs1318822
• NM_001166108.2:c.1965-47584C>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.1965-47584C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,000 control chromosomes in the GnomAD database, including 33,779 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 0.66 (33779 hom., cov: 32)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	NM_001166108.2	MANE Select	c.1965-47584C>T		intron	N/A	NP_001159580.1
	PALLD	NM_016081.4		c.1965-47584C>T		intron	N/A	NP_057165.3
	PALLD	NM_001166109.2		c.819-47584C>T		intron	N/A	NP_001159581.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-47584C>T		intron	N/A	ENSP00000425556.1
	PALLD	ENST00000261509.10	TSL:1	c.1965-47584C>T		intron	N/A	ENSP00000261509.6
	PALLD	ENST00000507735.6	TSL:1	c.-170+11167C>T		intron	N/A	ENSP00000424016.1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100023 AN: 151884 Hom.: 33737 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.659 AC: 100117 AN: 152000 Hom.: 33779 Cov.: 32 AF XY: 0.651 AC XY: 48384 AN XY: 74282

African (AFR) AF: 0.765 AC: 31687 AN: 41434

American (AMR) AF: 0.537 AC: 8207 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2371 AN: 3472

East Asian (EAS) AF: 0.243 AC: 1255 AN: 5170

South Asian (SAS) AF: 0.633 AC: 3048 AN: 4818

European-Finnish (FIN) AF: 0.612 AC: 6451 AN: 10536

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 44987 AN: 67970

Other (OTH) AF: 0.657 AC: 1387 AN: 2110

Alfa AF: 0.655 Hom.: 143579

Bravo AF: 0.654

Asia WGS AF: 0.455 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.96
DANN	Benign	0.32
PhyloP100		-0.29
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: rs1318822; hg19: chr4-169764489;