rs6819031

Variant names:

• chr4-168906467-G-A
• rs6819031
• NM_001166108.2:c.2622+2561G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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]

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	NM_001166108.2	MANE Select	c.2622+2561G>A		intron	N/A	NP_001159580.1
	PALLD	NM_016081.4		c.2571+2561G>A		intron	N/A	NP_057165.3
	PALLD	NM_001166109.2		c.1425+2561G>A		intron	N/A	NP_001159581.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.2622+2561G>A		intron	N/A	ENSP00000425556.1
	PALLD	ENST00000261509.10	TSL:1	c.2571+2561G>A		intron	N/A	ENSP00000261509.6
	PALLD	ENST00000507735.6	TSL:1	c.1110+2561G>A		intron	N/A	ENSP00000424016.1

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

African (AFR) AF: 0.294 AC: 12172 AN: 41418

American (AMR) AF: 0.109 AC: 1666 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3468

East Asian (EAS) AF: 0.0775 AC: 402 AN: 5186

South Asian (SAS) AF: 0.102 AC: 490 AN: 4816

European-Finnish (FIN) AF: 0.102 AC: 1079 AN: 10568

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8444 AN: 67982

Other (OTH) AF: 0.160 AC: 337 AN: 2112

Alfa AF: 0.132 Hom.: 2570

Bravo AF: 0.172

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0060
DANN	Benign	0.13
PhyloP100		-0.69
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: rs6819031; hg19: chr4-169827618;