4-168742464-T-G

Position:

• chr4-168742464-T-G

Variant summary

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

The NM_001166108.2(PALLD):​c.1964+30541T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,926 control chromosomes in the GnomAD database, including 21,326 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 0.53 (21326 hom., cov: 32)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALLD	NM_001166108.2	c.1964+30541T>G		intron_variant		ENST00000505667.6	NP_001159580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6	c.1964+30541T>G		intron_variant		1	NM_001166108.2	ENSP00000425556	A2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80131 AN: 151808 Hom.: 21313 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.528 AC: 80183 AN: 151926 Hom.: 21326 Cov.: 32 AF XY: 0.527 AC XY: 39132 AN XY: 74256

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.497

Alfa AF: 0.517 Hom.: 19633

Bravo AF: 0.532

Asia WGS AF: 0.597 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.44

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: rs6811238; hg19: chr4-169663615;