4-168877827-C-A

Variant names:

• chr4-168877827-C-A
• rs186421929
• ENST00000507735.6:c.-65C>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001166110.2(PALLD):​c.-65C>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00139 in 1,306,594 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (29 hom.)
• Consequence: PALLD NM_001166110.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.80
• Publications: 2 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]

LOC102723331 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.158).
• BP6: Variant 4-168877827-C-A is Benign according to our data. Variant chr4-168877827-C-A is described in ClinVar as Benign. ClinVar VariationId is 1232402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00171 (260/151756) while in subpopulation EAS AF = 0.0357 (184/5152). AF 95% confidence interval is 0.0315. There are 2 homozygotes in GnomAd4. There are 129 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 260 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.1965-13095C>A		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_001166110.2		c.-65C>A		5_prime_UTR	Exon 2 of 12	NP_001159582.1	Q8WX93-4
	PALLD	NM_016081.4		c.1965-13095C>A		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.-65C>A		5_prime_UTR	Exon 2 of 12	ENSP00000424016.1	Q8WX93-4
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-13095C>A		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.1965-13095C>A		intron	N/A	ENSP00000261509.6	Q8WX93-2

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 260 AN: 151648 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0356

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00212

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000339

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00153 AC: 41 AN: 26756 AF XY: 0.00131

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00197

Gnomad EAS exome AF: 0.0406

Gnomad FIN exome AF: 0.000940

Gnomad NFE exome AF: 0.000407

Gnomad OTH exome AF: 0.00120

GnomAD4 exome AF: 0.00134 AC: 1550 AN: 1154838 Hom.: 29 Cov.: 30 AF XY: 0.00137 AC XY: 767 AN XY: 560700

African (AFR) AF: 0.0000854 AC: 2 AN: 23422

American (AMR) AF: 0.0000807 AC: 1 AN: 12390

Ashkenazi Jewish (ASJ) AF: 0.000502 AC: 8 AN: 15934

East Asian (EAS) AF: 0.0437 AC: 1108 AN: 25330

South Asian (SAS) AF: 0.00355 AC: 138 AN: 38868

European-Finnish (FIN) AF: 0.00240 AC: 61 AN: 25434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4418

European-Non Finnish (NFE) AF: 0.000143 AC: 138 AN: 962716

Other (OTH) AF: 0.00203 AC: 94 AN: 46326

GnomAD4 genome AF: 0.00171 AC: 260 AN: 151756 Hom.: 2 Cov.: 32 AF XY: 0.00174 AC XY: 129 AN XY: 74192

African (AFR) AF: 0.000193 AC: 8 AN: 41494

American (AMR) AF: 0.000197 AC: 3 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.0357 AC: 184 AN: 5152

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4824

European-Finnish (FIN) AF: 0.00212 AC: 22 AN: 10396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000339 AC: 23 AN: 67868

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000477 Hom.: 0

Bravo AF: 0.00187

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Uncertain	1.0
PhyloP100		6.8
Mutation Taster		=77/23	polymorphism

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: rs186421929; hg19: chr4-169798978;