2-69955673-T-C

Variant names:

• chr2-69955673-T-C
• rs7583236
• XR_007088762.1:n.29T>C

Variant summary

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

The XR_007088762.1(LOC124906177):​n.29T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,180 control chromosomes in the GnomAD database, including 2,514 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 0.16 (2514 hom., cov: 32)
• Consequence: LOC124906177 XR_007088762.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 9 publications found

Genes affected

LOC124906177 (HGNC:):

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000812975.1. 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.1100+19882A>G		intron	N/A
	ASPRV1	NR_170376.1		n.701-11755A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000305793	ENST00000812975.1		n.60+1322T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24849 AN: 152062 Hom.: 2508 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.164 AC: 24883 AN: 152180 Hom.: 2514 Cov.: 32 AF XY: 0.168 AC XY: 12490 AN XY: 74378

African (AFR) AF: 0.258 AC: 10702 AN: 41502

American (AMR) AF: 0.192 AC: 2938 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3468

East Asian (EAS) AF: 0.291 AC: 1507 AN: 5180

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1306 AN: 10596

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0937 AC: 6373 AN: 68012

Other (OTH) AF: 0.153 AC: 324 AN: 2114

Alfa AF: 0.116 Hom.: 4992

Bravo AF: 0.174

Asia WGS AF: 0.254 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.69
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs7583236; hg19: chr2-70182805;