4-168877827-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001166110.2(PALLD):​c.-65C>G variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000693 in 1,306,592 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00054 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (1 hom.)
• Consequence: PALLD NM_001166110.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.199).
• BS2: High AC in GnomAd4 at 82 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>G		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_001166110.2		c.-65C>G		5_prime_UTR	Exon 2 of 12	NP_001159582.1	Q8WX93-4
	PALLD	NM_016081.4		c.1965-13095C>G		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>G		5_prime_UTR	Exon 2 of 12	ENSP00000424016.1	Q8WX93-4
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.1965-13095C>G		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.1965-13095C>G		intron	N/A	ENSP00000261509.6	Q8WX93-2

Frequencies

GnomAD3 genomes AF: 0.000541 AC: 82 AN: 151648 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000677

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000788

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000457

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000710 AC: 19 AN: 26756 AF XY: 0.000562

Gnomad AFR exome AF: 0.00222

Gnomad AMR exome AF: 0.000255

Gnomad ASJ exome AF: 0.00344

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000570

Gnomad OTH exome AF: 0.00239

GnomAD4 exome AF: 0.000714 AC: 824 AN: 1154836 Hom.: 1 Cov.: 30 AF XY: 0.000717 AC XY: 402 AN XY: 560700

African (AFR) AF: 0.000427 AC: 10 AN: 23422

American (AMR) AF: 0.00113 AC: 14 AN: 12390

Ashkenazi Jewish (ASJ) AF: 0.00383 AC: 61 AN: 15934

East Asian (EAS) AF: 0.000158 AC: 4 AN: 25332

South Asian (SAS) AF: 0.0000515 AC: 2 AN: 38868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25434

Middle Eastern (MID) AF: 0.000679 AC: 3 AN: 4418

European-Non Finnish (NFE) AF: 0.000720 AC: 693 AN: 962714

Other (OTH) AF: 0.000799 AC: 37 AN: 46324

GnomAD4 genome AF: 0.000540 AC: 82 AN: 151756 Hom.: 0 Cov.: 32 AF XY: 0.000472 AC XY: 35 AN XY: 74192

African (AFR) AF: 0.000675 AC: 28 AN: 41494

American (AMR) AF: 0.000787 AC: 12 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10396

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

European-Non Finnish (NFE) AF: 0.000457 AC: 31 AN: 67868

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Uncertain	1.0
PhyloP100		6.8

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: rs186421929; hg19: chr4-169798978;