rs200020758

Variant names:

• chr4-168878233-A-ACCG
• rs200020758
• ENST00000507735.6:c.347_349dupCGC

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BS1 BS2

The NM_001166110.2(PALLD):​c.347_349dupCGC​(p.Pro116dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00166 in 1,497,616 control chromosomes in the GnomAD database, including 36 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0099 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00080 (17 hom.)
• Consequence: PALLD NM_001166110.2 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 5.32
• Publications: 0 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 -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001166110.2. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 4-168878233-A-ACCG is Benign according to our data. Variant chr4-168878233-A-ACCG is described in ClinVar as Benign. ClinVar VariationId is 416233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00987 (1399/141794) while in subpopulation AFR AF = 0.0346 (1304/37698). AF 95% confidence interval is 0.033. There are 19 homozygotes in GnomAd4. There are 668 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1399 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166110.2. 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.1965-12684_1965-12682dupCGC		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_001166110.2		c.347_349dupCGC	p.Pro116dup	disruptive_inframe_insertion	Exon 2 of 12	NP_001159582.1	Q8WX93-4
	PALLD	NM_016081.4		c.1965-12684_1965-12682dupCGC		intron	N/A	NP_057165.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000507735.6	TSL:1	c.347_349dupCGC	p.Pro116dup	disruptive_inframe_insertion	Exon 2 of 12	ENSP00000424016.1	Q8WX93-4
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12684_1965-12682dupCGC		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.1965-12684_1965-12682dupCGC		intron	N/A	ENSP00000261509.6	Q8WX93-2

Frequencies

GnomAD3 genomes AF: 0.00983 AC: 1393 AN: 141710 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000240

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000260

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00111 AC: 127 AN: 113988 AF XY: 0.000715

Gnomad AFR exome AF: 0.0256

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000702

Gnomad OTH exome AF: 0.00172

GnomAD4 exome AF: 0.000800 AC: 1084 AN: 1355822 Hom.: 17 Cov.: 46 AF XY: 0.000670 AC XY: 448 AN XY: 669068

African (AFR) AF: 0.0297 AC: 856 AN: 28830

American (AMR) AF: 0.00174 AC: 59 AN: 33898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24072

East Asian (EAS) AF: 0.00 AC: 0 AN: 33014

South Asian (SAS) AF: 0.0000520 AC: 4 AN: 76970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32838

Middle Eastern (MID) AF: 0.00267 AC: 11 AN: 4126

European-Non Finnish (NFE) AF: 0.0000347 AC: 37 AN: 1065838

Other (OTH) AF: 0.00208 AC: 117 AN: 56236

GnomAD4 genome AF: 0.00987 AC: 1399 AN: 141794 Hom.: 19 Cov.: 32 AF XY: 0.00970 AC XY: 668 AN XY: 68884

African (AFR) AF: 0.0346 AC: 1304 AN: 37698

American (AMR) AF: 0.00450 AC: 64 AN: 14216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 4606

South Asian (SAS) AF: 0.000240 AC: 1 AN: 4162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.000260 AC: 17 AN: 65390

Other (OTH) AF: 0.00663 AC: 13 AN: 1962

Alfa AF: 0.00554 Hom.: 0

Asia WGS AF: 0.00145 AC: 5 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	PALLD-related disorder (1)
-	-	1	Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3
Mutation Taster		=67/33	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200020758; hg19: chr4-169799384;