chr2-69946497-T-C

Variant names:

• chr2-69946497-T-C
• rs10496176
• NR_170375.1:n.1101-13304A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_170375.1(ASPRV1):​n.1101-13304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,176 control chromosomes in the GnomAD database, including 3,839 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 0.20 (3839 hom., cov: 32)
• Consequence: ASPRV1 NR_170375.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 16 publications found

Genes affected

ASPRV1 (HGNC:26321): (aspartic peptidase retroviral like 1) Filaggrin is a structural protein that is crucial for in the development and maintenance of the skin barrier. This gene encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. Expression is found primarily in the epidermis and inner root sheath of hair follicles. [provided by RefSeq, May 2017]

ASPRV1 Gene-Disease associations (from GenCC):

• ichthyosis, lamellar, autosomal dominant

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_170375.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASPRV1	NR_170375.1		n.1101-13304A>G		intron	N/A
	ASPRV1	NR_170376.1		n.701-2579A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30384 AN: 152058 Hom.: 3823 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.200 AC: 30436 AN: 152176 Hom.: 3839 Cov.: 32 AF XY: 0.207 AC XY: 15377 AN XY: 74412

African (AFR) AF: 0.173 AC: 7186 AN: 41518

American (AMR) AF: 0.420 AC: 6422 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 817 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2204 AN: 5170

South Asian (SAS) AF: 0.236 AC: 1141 AN: 4830

European-Finnish (FIN) AF: 0.173 AC: 1832 AN: 10592

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10166 AN: 67996

Other (OTH) AF: 0.233 AC: 492 AN: 2112

Alfa AF: 0.182 Hom.: 9820

Bravo AF: 0.224

Asia WGS AF: 0.309 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.83
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs10496176; hg19: chr2-70173629; COSMIC: COSV52479749;