rs1071738

Variant names:

• chr4-168928238-C-G
• rs1071738
• NM_001166108.2:c.*2058C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-168928238-C-G
• chr4-168928238-C-A
• chr4-168928238-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001166108.2(PALLD):​c.*2058C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 183,792 control chromosomes in the GnomAD database, including 32,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (24922 hom., cov: 31)
  • Exomes 𝑓: 0.66 (7246 hom.)
• Consequence: PALLD NM_001166108.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.32
• Publications: 28 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 4-168928238-C-G is Benign according to our data. Variant chr4-168928238-C-G is described in ClinVar as Benign. ClinVar VariationId is 348069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 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.*2058C>G		3_prime_UTR	Exon 22 of 22	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.*2058C>G		3_prime_UTR	Exon 21 of 21	NP_057165.3
	PALLD	NM_001166109.2		c.*1853C>G		3_prime_UTR	Exon 19 of 19	NP_001159581.1	Q8WX93-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.*2058C>G		3_prime_UTR	Exon 22 of 22	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.*2058C>G		3_prime_UTR	Exon 21 of 21	ENSP00000261509.6	Q8WX93-2
	PALLD	ENST00000507735.6	TSL:1	c.*1853C>G		3_prime_UTR	Exon 12 of 12	ENSP00000424016.1	Q8WX93-4

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80446 AN: 151862 Hom.: 24909 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.663 AC: 21088 AN: 31812 Hom.: 7246 Cov.: 0 AF XY: 0.666 AC XY: 9782 AN XY: 14684

African (AFR) AF: 0.200 AC: 219 AN: 1096

American (AMR) AF: 0.649 AC: 484 AN: 746

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 1278 AN: 2042

East Asian (EAS) AF: 0.875 AC: 5322 AN: 6082

South Asian (SAS) AF: 0.722 AC: 182 AN: 252

European-Finnish (FIN) AF: 0.718 AC: 319 AN: 444

Middle Eastern (MID) AF: 0.524 AC: 110 AN: 210

European-Non Finnish (NFE) AF: 0.634 AC: 11621 AN: 18338

Other (OTH) AF: 0.597 AC: 1553 AN: 2602

GnomAD4 genome AF: 0.529 AC: 80470 AN: 151980 Hom.: 24922 Cov.: 31 AF XY: 0.540 AC XY: 40122 AN XY: 74290

African (AFR) AF: 0.188 AC: 7786 AN: 41394

American (AMR) AF: 0.616 AC: 9408 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2115 AN: 3464

East Asian (EAS) AF: 0.884 AC: 4572 AN: 5172

South Asian (SAS) AF: 0.697 AC: 3361 AN: 4820

European-Finnish (FIN) AF: 0.732 AC: 7730 AN: 10554

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43629 AN: 67982

Other (OTH) AF: 0.551 AC: 1161 AN: 2108

Alfa AF: 0.463 Hom.: 1575

Bravo AF: 0.507

Asia WGS AF: 0.767 AC: 2664 AN: 3476

ClinVar

ClinVar submissions

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	-0.33
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		3.3
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: rs1071738; hg19: chr4-169849389;