rs113515140

Variant names:

• chr4-168926209-G-A
• rs113515140
• NM_001166108.2:c.*33-4G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-168926209-G-A
• chr4-168926209-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001166108.2(PALLD):​c.*33-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,508,264 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00092 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: PALLD NM_001166108.2 splice_region, intron
• Scores: Splicing: ADA: 0.00007353
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.185
• Publications: 0 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-168926209-G-A is Benign according to our data. Variant chr4-168926209-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 215802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 140 AD gene.

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.*33-4G>A		splice_region intron	N/A	NP_001159580.1
	PALLD	NM_016081.4		c.*33-4G>A		splice_region intron	N/A	NP_057165.3
	PALLD	NM_001166109.2		c.2162-4G>A		splice_region intron	N/A	NP_001159581.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.*33-4G>A		splice_region intron	N/A	ENSP00000425556.1
	PALLD	ENST00000261509.10	TSL:1	c.*33-4G>A		splice_region intron	N/A	ENSP00000261509.6
	PALLD	ENST00000507735.6	TSL:1	c.1847-4G>A		splice_region intron	N/A	ENSP00000424016.1

Frequencies

GnomAD3 genomes AF: 0.000910 AC: 138 AN: 151700 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000164 AC: 21 AN: 127750 AF XY: 0.0000732

Gnomad AFR exome AF: 0.00294

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000103 AC: 140 AN: 1356446 Hom.: 1 Cov.: 30 AF XY: 0.0000974 AC XY: 65 AN XY: 667214

African (AFR) AF: 0.00344 AC: 104 AN: 30194

American (AMR) AF: 0.00 AC: 0 AN: 30736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24036

East Asian (EAS) AF: 0.00 AC: 0 AN: 35174

South Asian (SAS) AF: 0.00 AC: 0 AN: 74466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1065204

Other (OTH) AF: 0.000619 AC: 35 AN: 56538

GnomAD4 genome AF: 0.000922 AC: 140 AN: 151818 Hom.: 1 Cov.: 32 AF XY: 0.000768 AC XY: 57 AN XY: 74192

African (AFR) AF: 0.00329 AC: 136 AN: 41364

American (AMR) AF: 0.000262 AC: 4 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000434 Hom.: 0

Bravo AF: 0.000990

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	PALLD-related disorder (1)
-	-	1	Pancreatic adenocarcinoma (1)
-	-	1	Pancreatic cancer, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.66
PhyloP100		-0.18

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000074
dbscSNV1_RF	Benign	0.0
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: rs113515140; hg19: chr4-169847360;