4-168878150-TCGCCCC-T

Variant names:

• chr4-168878150-TCGCCCC-T
• rs730882137
• ENST00000507735.6:c.270_275delCCCGCC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000505667.6(PALLD):​c.1965-12761_1965-12756delCCCGCC variant causes a intron change. The variant allele was found at a frequency of 0.00007 in 1,486,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: PALLD ENST00000505667.6 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.33
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000505667.6. 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.1965-12761_1965-12756delCCCGCC		intron	N/A	NP_001159580.1
	PALLD	NM_001166110.2		c.270_275delCCCGCC	p.Pro91_Pro92del	disruptive_inframe_deletion	Exon 2 of 12	NP_001159582.1
	PALLD	NM_016081.4		c.1965-12761_1965-12756delCCCGCC		intron	N/A	NP_057165.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000507735.6	TSL:1	c.270_275delCCCGCC	p.Pro91_Pro92del	disruptive_inframe_deletion	Exon 2 of 12	ENSP00000424016.1
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12761_1965-12756delCCCGCC		intron	N/A	ENSP00000425556.1
	PALLD	ENST00000261509.10	TSL:1	c.1965-12761_1965-12756delCCCGCC		intron	N/A	ENSP00000261509.6

Frequencies

GnomAD3 genomes AF: 0.0000869 AC: 13 AN: 149544 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000497

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000119

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000890 AC: 8 AN: 89912 AF XY: 0.0000988

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000382

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000907

Gnomad OTH exome AF: 0.000371

GnomAD4 exome AF: 0.0000681 AC: 91 AN: 1337022 Hom.: 0 AF XY: 0.0000728 AC XY: 48 AN XY: 659012

African (AFR) AF: 0.0000741 AC: 2 AN: 27004

American (AMR) AF: 0.00 AC: 0 AN: 30162

Ashkenazi Jewish (ASJ) AF: 0.0000424 AC: 1 AN: 23600

East Asian (EAS) AF: 0.00 AC: 0 AN: 30602

South Asian (SAS) AF: 0.0000268 AC: 2 AN: 74532

European-Finnish (FIN) AF: 0.0000905 AC: 3 AN: 33152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4026

European-Non Finnish (NFE) AF: 0.0000709 AC: 75 AN: 1058360

Other (OTH) AF: 0.000144 AC: 8 AN: 55584

GnomAD4 genome AF: 0.0000869 AC: 13 AN: 149652 Hom.: 0 Cov.: 32 AF XY: 0.0000820 AC XY: 6 AN XY: 73164

African (AFR) AF: 0.0000495 AC: 2 AN: 40376

American (AMR) AF: 0.000132 AC: 2 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5000

South Asian (SAS) AF: 0.000213 AC: 1 AN: 4690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000119 AC: 8 AN: 67306

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000869

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)
-	1	-	Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3
Mutation Taster		=141/59	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs730882137; hg19: chr4-169799301;