rs864622590

Variant names:

• chr4-168877981-G-A
• rs864622590
• ENST00000507735.6:c.90G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-168877981-G-A
• chr4-168877981-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The ENST00000505667.6(PALLD):​c.1965-12941G>A variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000815 in 1,349,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000081 (0 hom.)
• Consequence: PALLD ENST00000505667.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.24
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 4-168877981-G-A is Benign according to our data. Variant chr4-168877981-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 220583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAdExome4 at 11 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.1965-12941G>A		intron	N/A	NP_001159580.1
	PALLD	NM_001166110.2		c.90G>A	p.Gln30Gln	synonymous	Exon 2 of 12	NP_001159582.1
	PALLD	NM_016081.4		c.1965-12941G>A		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.90G>A	p.Gln30Gln	synonymous	Exon 2 of 12	ENSP00000424016.1
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-12941G>A		intron	N/A	ENSP00000425556.1
	PALLD	ENST00000261509.10	TSL:1	c.1965-12941G>A		intron	N/A	ENSP00000261509.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000815 AC: 11 AN: 1349984 Hom.: 0 Cov.: 31 AF XY: 0.00000450 AC XY: 3 AN XY: 665972

African (AFR) AF: 0.00 AC: 0 AN: 27584

American (AMR) AF: 0.00 AC: 0 AN: 32372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24018

East Asian (EAS) AF: 0.00 AC: 0 AN: 31436

South Asian (SAS) AF: 0.00 AC: 0 AN: 76464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5392

European-Non Finnish (NFE) AF: 0.0000103 AC: 11 AN: 1063130

Other (OTH) AF: 0.00 AC: 0 AN: 56316

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

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
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.94
PhyloP100		7.2

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: rs864622590; hg19: chr4-169799132;