rs2585417

chr20-54227260-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000441080.2(PFDN4):c.*63-693G>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,858 control chromosomes in the GnomAD database, including 24,549 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24549 hom., cov: 31)
• Consequence: PFDN4 ENST00000441080.2 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

Genes affected

PFDN4 (HGNC:8868): (prefoldin subunit 4) This gene encodes a member of the prefoldin beta subunit family. The encoded protein is one of six subunits of prefoldin, a molecular chaperone complex that binds and stabilizes newly synthesized polypeptides, thereby allowing them to fold correctly. The complex, consisting of two alpha and four beta subunits, forms a double beta barrel assembly with six protruding coiled-coils. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFDN4	ENST00000441080.2	c.*63-693G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84624 AN: 151740 Hom.: 24502 Cov.: 31

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.558 AC: 84720 AN: 151858 Hom.: 24549 Cov.: 31 AF XY: 0.554 AC XY: 41101 AN XY: 74208

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.529

Alfa AF: 0.515 Hom.: 20024

Bravo AF: 0.554

Asia WGS AF: 0.419 AC: 1456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.0
Dann	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2585417; hg19: chr20-52843799;