4-168878150-TCGCCCC-TCGCCCCCGCCCC

Variant names:

• chr4-168878150-T-TCGCCCC
• rs730882137
• ENST00000507735.6:c.270_275dupCCCGCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_001166110.2(PALLD):​c.270_275dupCCCGCC​(p.Pro91_Pro92dup) variant causes a disruptive inframe insertion change. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0082 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (13 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALLD NM_001166110.2 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.82

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 -8 ACMG points.

• BP6: Variant 4-168878150-T-TCGCCCC is Benign according to our data. Variant chr4-168878150-T-TCGCCCC is described in ClinVar as [Benign]. Clinvar id is 220482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALLD	NM_001166108.2	c.1965-12761_1965-12756dupCCCGCC		intron_variant	Intron 10 of 21	ENST00000505667.6	NP_001159580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALLD	ENST00000505667.6	c.1965-12761_1965-12756dupCCCGCC		intron_variant	Intron 10 of 21	1	NM_001166108.2	ENSP00000425556.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1225 AN: 149428 Hom.: 10 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00416

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000426

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00968

Gnomad NFE AF: 0.000208

Gnomad OTH AF: 0.00436

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000814 AC: 1088 AN: 1336966 Hom.: 13 Cov.: 30 AF XY: 0.000724 AC XY: 477 AN XY: 658994

Gnomad4 AFR exome AF: 0.0278

Gnomad4 AMR exome AF: 0.000597

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000654

Gnomad4 SAS exome AF: 0.0000537

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000171

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00820 AC: 1226 AN: 149536 Hom.: 10 Cov.: 32 AF XY: 0.00826 AC XY: 604 AN XY: 73108

Gnomad4 AFR AF: 0.0282

Gnomad4 AMR AF: 0.00416

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000208

Gnomad4 OTH AF: 0.00431

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Oct 29, 2024

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Pancreatic adenocarcinoma Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PALLD-related disorder Benign:1

Mar 06, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs730882137; hg19: chr4-169799301;