rs6822949

Variant names:

• chr4-168736422-G-C
• rs6822949
• NM_001166108.2:c.1964+24499G>C

Variant summary

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

The NM_001166108.2(PALLD):​c.1964+24499G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0602 in 152,206 control chromosomes in the GnomAD database, including 736 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 0.060 (736 hom., cov: 32)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 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.1964+24499G>C		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.1964+24499G>C		intron	N/A	NP_057165.3
	PALLD	NM_001166109.2		c.818+24499G>C		intron	N/A	NP_001159581.1	Q8WX93-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1964+24499G>C		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.1964+24499G>C		intron	N/A	ENSP00000261509.6	Q8WX93-2
	PALLD	ENST00000968439.1		c.1964+24499G>C		intron	N/A	ENSP00000638498.1

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9126 AN: 152088 Hom.: 730 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.00942

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00628

Gnomad OTH AF: 0.0474

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

GnomAD4 genome AF: 0.0602 AC: 9156 AN: 152206 Hom.: 736 Cov.: 32 AF XY: 0.0613 AC XY: 4565 AN XY: 74426

African (AFR) AF: 0.149 AC: 6205 AN: 41506

American (AMR) AF: 0.0338 AC: 517 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3464

East Asian (EAS) AF: 0.322 AC: 1661 AN: 5160

South Asian (SAS) AF: 0.0178 AC: 86 AN: 4822

European-Finnish (FIN) AF: 0.00942 AC: 100 AN: 10614

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00628 AC: 427 AN: 68020

Other (OTH) AF: 0.0464 AC: 98 AN: 2112

Alfa AF: 0.0341 Hom.: 35

Bravo AF: 0.0684

Asia WGS AF: 0.125 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.72
DANN	Benign	0.54
PhyloP100		-0.79
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: rs6822949; hg19: chr4-169657573;