rs4692552

Positions:

• chr4-168843480-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001166108.2(PALLD):​c.1965-47442T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,148 control chromosomes in the GnomAD database, including 3,101 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 0.18 (3101 hom., cov: 32)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.863

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALLD	NM_001166108.2	c.1965-47442T>C		intron_variant		ENST00000505667.6	NP_001159580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6	c.1965-47442T>C		intron_variant		1	NM_001166108.2	ENSP00000425556	A2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28093 AN: 152030 Hom.: 3102 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.185 AC: 28097 AN: 152148 Hom.: 3101 Cov.: 32 AF XY: 0.181 AC XY: 13483 AN XY: 74374

Gnomad4 AFR AF: 0.0924

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.190

Alfa AF: 0.242 Hom.: 3933

Bravo AF: 0.175

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs4692552; hg19: chr4-169764631;