4-168511143-C-T

Position:

• chr4-168511143-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001166108.2(PALLD):​c.-82-280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 152,162 control chromosomes in the GnomAD database, including 339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.059 (339 hom., cov: 32)
• Consequence: PALLD NM_001166108.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.636

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]

LOC107986198 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-168511143-C-T is Benign according to our data. Variant chr4-168511143-C-T is described in ClinVar as [Benign]. Clinvar id is 1295087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALLD	NM_001166108.2	c.-82-280C>T		intron_variant		ENST00000505667.6
LOC107986198	XR_001741448.3	n.281-18258G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALLD	ENST00000505667.6	c.-82-280C>T		intron_variant		1	NM_001166108.2	A2

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 9003 AN: 152044 Hom.: 341 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0745

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0477

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0721

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0591 AC: 8996 AN: 152162 Hom.: 339 Cov.: 32 AF XY: 0.0608 AC XY: 4519 AN XY: 74366

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0744

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.0479

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.0721

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0601 Hom.: 54

Bravo AF: 0.0567

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.58
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs75967573; hg19: chr4-169432294;