4-168756241-A-G

Variant names:

• chr4-168756241-A-G
• rs12510359
• NM_001166108.2:c.1964+44318A>G

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.1964+44318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 187,304 control chromosomes in the GnomAD database, including 25,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (21663 hom., cov: 32)
  • Exomes 𝑓: 0.47 (4270 hom.)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.41
• Publications: 5 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]

RPL9P16 (HGNC:36851): (ribosomal protein L9 pseudogene 16)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 4-168756241-A-G is Benign according to our data. Variant chr4-168756241-A-G is described in ClinVar as Benign. ClinVar VariationId is 1164338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 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.1964+44318A>G		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.1964+44318A>G		intron	N/A	NP_057165.3
	PALLD	NM_001166109.2		c.818+44318A>G		intron	N/A	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.1964+44318A>G		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.1964+44318A>G		intron	N/A	ENSP00000261509.6	Q8WX93-2
	PALLD	ENST00000968439.1		c.1964+44318A>G		intron	N/A	ENSP00000638498.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76235 AN: 151998 Hom.: 21664 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.472 AC: 16621 AN: 35188 Hom.: 4270 Cov.: 0 AF XY: 0.449 AC XY: 8827 AN XY: 19650

African (AFR) AF: 0.128 AC: 59 AN: 460

American (AMR) AF: 0.333 AC: 356 AN: 1068

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 246 AN: 696

East Asian (EAS) AF: 0.0955 AC: 59 AN: 618

South Asian (SAS) AF: 0.325 AC: 2264 AN: 6968

European-Finnish (FIN) AF: 0.648 AC: 2225 AN: 3432

Middle Eastern (MID) AF: 0.344 AC: 64 AN: 186

European-Non Finnish (NFE) AF: 0.527 AC: 10392 AN: 19734

Other (OTH) AF: 0.472 AC: 956 AN: 2026

GnomAD4 genome AF: 0.501 AC: 76249 AN: 152116 Hom.: 21663 Cov.: 32 AF XY: 0.500 AC XY: 37147 AN XY: 74360

African (AFR) AF: 0.256 AC: 10630 AN: 41494

American (AMR) AF: 0.509 AC: 7778 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1784 AN: 3468

East Asian (EAS) AF: 0.164 AC: 851 AN: 5180

South Asian (SAS) AF: 0.465 AC: 2243 AN: 4822

European-Finnish (FIN) AF: 0.697 AC: 7371 AN: 10574

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44024 AN: 67980

Other (OTH) AF: 0.504 AC: 1065 AN: 2112

Alfa AF: 0.591 Hom.: 16747

Bravo AF: 0.476

Asia WGS AF: 0.312 AC: 1088 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Pancreatic adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.1
DANN	Benign	0.82
PhyloP100		1.4
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: rs12510359; hg19: chr4-169677392; COSMIC: COSV54981504;