rs1136603

Variant names:

• chr4-168928086-G-A
• rs1136603
• NM_001166108.2:c.*1906G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001166108.2(PALLD):​c.*1906G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 195,530 control chromosomes in the GnomAD database, including 1,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1384 hom., cov: 33)
  • Exomes 𝑓: 0.11 (286 hom.)
• Consequence: PALLD NM_001166108.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.95
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-168928086-G-A is Benign according to our data. Variant chr4-168928086-G-A is described in ClinVar as Benign. ClinVar VariationId is 348067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166108.2. 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.*1906G>A		3_prime_UTR	Exon 22 of 22	NP_001159580.1
	PALLD	NM_016081.4		c.*1906G>A		3_prime_UTR	Exon 21 of 21	NP_057165.3
	PALLD	NM_001166109.2		c.*1701G>A		3_prime_UTR	Exon 19 of 19	NP_001159581.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.*1906G>A		3_prime_UTR	Exon 22 of 22	ENSP00000425556.1
	PALLD	ENST00000261509.10	TSL:1	c.*1906G>A		3_prime_UTR	Exon 21 of 21	ENSP00000261509.6
	PALLD	ENST00000507735.6	TSL:1	c.*1701G>A		3_prime_UTR	Exon 12 of 12	ENSP00000424016.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19456 AN: 152022 Hom.: 1384 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.0728

Gnomad SAS AF: 0.0789

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.114 AC: 4926 AN: 43390 Hom.: 286 Cov.: 0 AF XY: 0.115 AC XY: 2309 AN XY: 20092

African (AFR) AF: 0.183 AC: 321 AN: 1750

American (AMR) AF: 0.0861 AC: 102 AN: 1184

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 250 AN: 2666

East Asian (EAS) AF: 0.0738 AC: 541 AN: 7330

South Asian (SAS) AF: 0.0513 AC: 20 AN: 390

European-Finnish (FIN) AF: 0.0852 AC: 38 AN: 446

Middle Eastern (MID) AF: 0.165 AC: 45 AN: 272

European-Non Finnish (NFE) AF: 0.125 AC: 3217 AN: 25762

Other (OTH) AF: 0.109 AC: 392 AN: 3590

GnomAD4 genome AF: 0.128 AC: 19472 AN: 152140 Hom.: 1384 Cov.: 33 AF XY: 0.124 AC XY: 9226 AN XY: 74378

African (AFR) AF: 0.182 AC: 7560 AN: 41478

American (AMR) AF: 0.0911 AC: 1392 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3472

East Asian (EAS) AF: 0.0729 AC: 378 AN: 5182

South Asian (SAS) AF: 0.0779 AC: 376 AN: 4824

European-Finnish (FIN) AF: 0.0757 AC: 802 AN: 10588

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8086 AN: 67998

Other (OTH) AF: 0.132 AC: 278 AN: 2106

Alfa AF: 0.119 Hom.: 832

Bravo AF: 0.132

Asia WGS AF: 0.0770 AC: 267 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Pancreatic cancer, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.68
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs1136603; hg19: chr4-169849237; COSMIC: COSV54993143; COSMIC: COSV54993143;