rs1059444

Variant names:

• chr4-168913983-A-G
• rs1059444
• NM_001166108.2:c.2679A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001166108.2(PALLD):​c.2679A>G​(p.Arg893Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,611,468 control chromosomes in the GnomAD database, including 9,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1389 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7735 hom.)
• Consequence: PALLD NM_001166108.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.523
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 4-168913983-A-G is Benign according to our data. Variant chr4-168913983-A-G is described in ClinVar as Benign. ClinVar VariationId is 348043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.523 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	NM_001166108.2	MANE Select	c.2679A>G	p.Arg893Arg	synonymous	Exon 16 of 22	NP_001159580.1
	PALLD	NM_016081.4		c.2628A>G	p.Arg876Arg	synonymous	Exon 15 of 21	NP_057165.3
	PALLD	NM_001166109.2		c.1482A>G	p.Arg494Arg	synonymous	Exon 14 of 19	NP_001159581.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.2679A>G	p.Arg893Arg	synonymous	Exon 16 of 22	ENSP00000425556.1
	PALLD	ENST00000261509.10	TSL:1	c.2628A>G	p.Arg876Arg	synonymous	Exon 15 of 21	ENSP00000261509.6
	PALLD	ENST00000507735.6	TSL:1	c.1167A>G	p.Arg389Arg	synonymous	Exon 7 of 12	ENSP00000424016.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18837 AN: 152094 Hom.: 1386 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0387

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.125

GnomAD2 exomes AF: 0.0916 AC: 23027 AN: 251416 AF XY: 0.0901

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.0695

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.0342

Gnomad FIN exome AF: 0.0454

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.0984 AC: 143631 AN: 1459256 Hom.: 7735 Cov.: 30 AF XY: 0.0971 AC XY: 70531 AN XY: 726090

African (AFR) AF: 0.202 AC: 6749 AN: 33400

American (AMR) AF: 0.0729 AC: 3260 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4787 AN: 26114

East Asian (EAS) AF: 0.0420 AC: 1665 AN: 39676

South Asian (SAS) AF: 0.0517 AC: 4456 AN: 86214

European-Finnish (FIN) AF: 0.0503 AC: 2689 AN: 53412

Middle Eastern (MID) AF: 0.147 AC: 845 AN: 5762

European-Non Finnish (NFE) AF: 0.102 AC: 112720 AN: 1109660

Other (OTH) AF: 0.107 AC: 6460 AN: 60294

GnomAD4 genome AF: 0.124 AC: 18853 AN: 152212 Hom.: 1389 Cov.: 32 AF XY: 0.118 AC XY: 8821 AN XY: 74442

African (AFR) AF: 0.198 AC: 8196 AN: 41484

American (AMR) AF: 0.111 AC: 1702 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3468

East Asian (EAS) AF: 0.0387 AC: 201 AN: 5188

South Asian (SAS) AF: 0.0533 AC: 257 AN: 4818

European-Finnish (FIN) AF: 0.0445 AC: 473 AN: 10632

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6982 AN: 68018

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.114 Hom.: 808

Bravo AF: 0.133

Asia WGS AF: 0.0430 AC: 150 AN: 3476

EpiCase AF: 0.114

EpiControl AF: 0.112

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Pancreatic cancer, susceptibility to, 1 (2)
-	-	1	not specified (1)
-	-	1	Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.52
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: rs1059444; hg19: chr4-169835134; COSMIC: COSV54980401; COSMIC: COSV54980401;