rs564343

Positions:

• chr11-66127695-A-G
• chr11-66127695-A-T

Variant summary

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

The ENST00000320580.9(PACS1):​c.356+56853A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,122 control chromosomes in the GnomAD database, including 18,091 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 0.47 (18091 hom., cov: 32)
• Consequence: PACS1 ENST00000320580.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

PACS1 (HGNC:30032): (phosphofurin acidic cluster sorting protein 1) This gene encodes a protein with a putative role in the localization of trans-Golgi network (TGN) membrane proteins. Mouse and rat homologs have been identified and studies of the homologous rat protein indicate a role in directing TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. In addition, the human protein plays a role in HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACS1	NM_018026.4	c.356+56853A>G		intron_variant		ENST00000320580.9	NP_060496.2
PACS1	XM_011545162.2	c.62+26821A>G		intron_variant			XP_011543464.2
PACS1	XM_011545164.3	c.17+43465A>G		intron_variant			XP_011543466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACS1	ENST00000320580.9	c.356+56853A>G		intron_variant		1	NM_018026.4	ENSP00000316454	P2
PACS1	ENST00000527380.1	c.62+26821A>G		intron_variant		4		ENSP00000432639
PACS1	ENST00000533756.5	c.47+6628A>G		intron_variant		4		ENSP00000437150
PACS1	ENST00000527224.1	n.480+56853A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.467 AC: 71035 AN: 152004 Hom.: 18095 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.467 AC: 71040 AN: 152122 Hom.: 18091 Cov.: 32 AF XY: 0.465 AC XY: 34612 AN XY: 74362

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.492

Alfa AF: 0.510 Hom.: 4877

Bravo AF: 0.443

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.059
DANN	Benign	0.49

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: rs564343; hg19: chr11-65895166;