rs7670597

Positions:

• chr4-168718175-G-A

Variant summary

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

The NM_001166108.2(PALLD):​c.1964+6252G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,002 control chromosomes in the GnomAD database, including 10,774 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 0.37 (10774 hom., cov: 32)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALLD	NM_001166108.2	c.1964+6252G>A		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+6252G>A		intron_variant		1	NM_001166108.2	ENSP00000425556.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55859 AN: 151884 Hom.: 10771 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.368 AC: 55872 AN: 152002 Hom.: 10774 Cov.: 32 AF XY: 0.366 AC XY: 27182 AN XY: 74292

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.429

Gnomad4 OTH AF: 0.359

Alfa AF: 0.413 Hom.: 18884

Bravo AF: 0.362

Asia WGS AF: 0.355 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.56

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: rs7670597; hg19: chr4-169639326;