rs1567375

chr11-119631766-A-Cchr11-119631766-A-G

Variant summary

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

The ENST00000706409.1(USP2-AS1):n.573-5159A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,026 control chromosomes in the GnomAD database, including 25,977 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 0.58 (25977 hom., cov: 32)
• Consequence: USP2-AS1 ENST00000706409.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

Genes affected

USP2-AS1 (HGNC:48673): (USP2 antisense RNA 1)

LOC105369520 (HGNC:):

NECTIN1 (HGNC:9706): (nectin cell adhesion molecule 1) This gene encodes an adhesion protein that plays a role in the organization of adherens junctions and tight junctions in epithelial and endothelial cells. The protein is a calcium(2+)-independent cell-cell adhesion molecule that belongs to the immunoglobulin superfamily and has 3 extracellular immunoglobulin-like loops, a single transmembrane domain (in some isoforms), and a cytoplasmic region. This protein acts as a receptor for glycoprotein D (gD) of herpes simplex viruses 1 and 2 (HSV-1, HSV-2), and pseudorabies virus (PRV) and mediates viral entry into epithelial and neuronal cells. Mutations in this gene cause cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1) as well as non-syndromic cleft lip with or without cleft palate (CL/P). Alternative splicing results in multiple transcript variants encoding proteins with distinct C-termini. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105369520	XR_001748413.1	n.60+330A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP2-AS1	ENST00000706409.1	n.573-5159A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88595 AN: 151908 Hom.: 25939 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.583 AC: 88685 AN: 152026 Hom.: 25977 Cov.: 32 AF XY: 0.580 AC XY: 43089 AN XY: 74310

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.568

Alfa AF: 0.547 Hom.: 9258

Bravo AF: 0.588

Asia WGS AF: 0.503 AC: 1747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.6
Dann	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1567375; hg19: chr11-119502477;