chr11-66222287-G-T

Position:

• chr11-66222287-G-T

Variant summary

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

The NM_018026.4(PACS1):​c.1293+1040G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,106 control chromosomes in the GnomAD database, including 1,412 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 0.11 (1412 hom., cov: 31)
• Consequence: PACS1 NM_018026.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACS1	NM_018026.4	c.1293+1040G>T		intron_variant		ENST00000320580.9	NP_060496.2
PACS1	XM_011545162.2	c.999+1040G>T		intron_variant			XP_011543464.2
PACS1	XM_011545164.3	c.954+1040G>T		intron_variant			XP_011543466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACS1	ENST00000320580.9	c.1293+1040G>T		intron_variant		1	NM_018026.4	ENSP00000316454.4

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17234 AN: 151988 Hom.: 1407 Cov.: 31

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.0862

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.113 AC: 17245 AN: 152106 Hom.: 1412 Cov.: 31 AF XY: 0.119 AC XY: 8831 AN XY: 74342

Gnomad4 AFR AF: 0.0274

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.0875

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.106

Alfa AF: 0.126 Hom.: 843

Bravo AF: 0.116

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.34

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: rs3741370; hg19: chr11-65989758;