rs6819031

Positions:

• chr4-168906467-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.2622+2561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,030 control chromosomes in the GnomAD database, including 2,621 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 0.17 (2621 hom., cov: 32)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685

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]

CBR4 (HGNC:25891): (carbonyl reductase 4) Enables several functions, including 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; NADPH binding activity; and NADPH dehydrogenase (quinone) activity. Involved in fatty acid biosynthetic process; glycoside metabolic process; and protein tetramerization. Located in mitochondrial matrix. Part of oxidoreductase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALLD	NM_001166108.2	c.2622+2561G>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.2622+2561G>A		intron_variant		1	NM_001166108.2	ENSP00000425556	A2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25171 AN: 151912 Hom.: 2615 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.166 AC: 25208 AN: 152030 Hom.: 2621 Cov.: 32 AF XY: 0.162 AC XY: 12049 AN XY: 74306

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0775

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.160

Alfa AF: 0.126 Hom.: 1784

Bravo AF: 0.172

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0060
DANN	Benign	0.13

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: rs6819031; hg19: chr4-169827618;