chr4-168511192-T-C

Variant names:

• chr4-168511192-T-C
• rs28415743
• NM_001166108.2:c.-82-231T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001166108.2(PALLD):​c.-82-231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,102 control chromosomes in the GnomAD database, including 6,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6720 hom., cov: 32)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240
• 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]

DDX60L (HGNC:26429): (DExD/H-box 60 like) This gene encodes a member of the DExD/H-box helicase family of proteins, a subset of the super family 2 helicases. Members of the DExD/H-box helicase family share a conserved functional core comprised of two RecA-like globular domains. These domains contain conserved motifs that mediate ATP binding, ATP hydrolysis, nucleic acid binding, and RNA unwinding. In addition to functions in RNA metabolism, members of this family are involved in anti-viral immunity and act as cytosolic sensors of viral nucleic acids. The protein encoded by this gene has been shown to inhibit hepatitis C virus replication in response to interferon stimulation in cell culture. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

LOC107986198 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-168511192-T-C is Benign according to our data. Variant chr4-168511192-T-C is described in ClinVar as Benign. ClinVar VariationId is 1252334.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 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.-82-231T>C		intron	N/A	NP_001159580.1	Q8WX93-9
	PALLD	NM_016081.4		c.-82-231T>C		intron	N/A	NP_057165.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALLD	ENST00000505667.6	TSL:1 MANE Select	c.-82-231T>C		intron	N/A	ENSP00000425556.1	Q8WX93-9
	PALLD	ENST00000261509.10	TSL:1	c.-82-231T>C		intron	N/A	ENSP00000261509.6	Q8WX93-2
	PALLD	ENST00000968439.1		c.-75-238T>C		intron	N/A	ENSP00000638498.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44782 AN: 151986 Hom.: 6713 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.281

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44810 AN: 152102 Hom.: 6720 Cov.: 32 AF XY: 0.294 AC XY: 21847 AN XY: 74354

African (AFR) AF: 0.250 AC: 10385 AN: 41508

American (AMR) AF: 0.242 AC: 3694 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 972 AN: 3464

East Asian (EAS) AF: 0.191 AC: 989 AN: 5182

South Asian (SAS) AF: 0.223 AC: 1073 AN: 4822

European-Finnish (FIN) AF: 0.396 AC: 4183 AN: 10560

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22453 AN: 67970

Other (OTH) AF: 0.277 AC: 585 AN: 2112

Alfa AF: 0.315 Hom.: 1014

Bravo AF: 0.281

Asia WGS AF: 0.199 AC: 692 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.40
PhyloP100		-0.024
PromoterAI		0.0040	Neutral
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: rs28415743; hg19: chr4-169432343;