rs863224384

Variant names:

• chr4-168878158-G-A
• rs863224384
• ENST00000507735.6:c.267G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-168878158-G-A
• chr4-168878158-G-C
• chr4-168878158-G-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The ENST00000507735.6(PALLD):​c.267G>A​(p.Pro89Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 790,240 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P89P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000077 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: PALLD ENST00000507735.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.98
• Publications: 1 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-168878158-G-A is Benign according to our data. Variant chr4-168878158-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3885280.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.98 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALLD	NM_001166108.2	c.1965-12764G>A		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.1965-12764G>A		intron_variant	Intron 10 of 21	1	NM_001166108.2	ENSP00000425556.1

Frequencies

GnomAD3 genomes AF: 0.00000769 AC: 1 AN: 129990 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000163

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000182 AC: 12 AN: 660250 Hom.: 0 Cov.: 30 AF XY: 0.00000910 AC XY: 3 AN XY: 329640

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11980

American (AMR) AF: 0.00 AC: 0 AN: 14550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11100

East Asian (EAS) AF: 0.000158 AC: 1 AN: 6340

South Asian (SAS) AF: 0.00 AC: 0 AN: 55044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1840

European-Non Finnish (NFE) AF: 0.0000210 AC: 11 AN: 523928

Other (OTH) AF: 0.00 AC: 0 AN: 24692

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000661514), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000769 AC: 1 AN: 129990 Hom.: 0 Cov.: 32 AF XY: 0.0000158 AC XY: 1 AN XY: 63220

African (AFR) AF: 0.00 AC: 0 AN: 33860

American (AMR) AF: 0.00 AC: 0 AN: 13226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3222

East Asian (EAS) AF: 0.00 AC: 0 AN: 3980

South Asian (SAS) AF: 0.00 AC: 0 AN: 3642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000163 AC: 1 AN: 61442

Other (OTH) AF: 0.00 AC: 0 AN: 1794

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 21, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.90
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs863224384; hg19: chr4-169799309;