5-148040461-A-G

Variant names:

• chr5-148040461-A-G
• rs1422982
• ENST00000521206.5:c.-183+14675A>G

Variant summary

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

The ENST00000521206.5(SPINK5):​c.-183+14675A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,816 control chromosomes in the GnomAD database, including 21,925 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 0.52 (21925 hom., cov: 31)
• Consequence: SPINK5 ENST00000521206.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651
• Publications: 1 publications found

Genes affected

SPINK5 (HGNC:15464): (serine peptidase inhibitor Kazal type 5) This gene encodes a multidomain serine protease inhibitor that contains 15 potential inhibitory domains. The encoded preproprotein is proteolytically processed to generate multiple protein products, which may exhibit unique activities and specificities. These proteins may play a role in skin and hair morphogenesis, as well as anti-inflammatory and antimicrobial protection of mucous epithelia. Mutations in this gene may result in Netherton syndrome, a disorder characterized by ichthyosis, defective cornification, and atopy. This gene is present in a gene cluster on chromosome 5. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

SPINK5 Gene-Disease associations (from GenCC):

• Netherton syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521206.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK5	ENST00000521206.5	TSL:4	c.-183+14675A>G		intron	N/A	ENSP00000430264.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79040 AN: 151698 Hom.: 21933 Cov.: 31

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.521 AC: 79044 AN: 151816 Hom.: 21925 Cov.: 31 AF XY: 0.530 AC XY: 39325 AN XY: 74180

African (AFR) AF: 0.327 AC: 13531 AN: 41424

American (AMR) AF: 0.626 AC: 9528 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1981 AN: 3466

East Asian (EAS) AF: 0.779 AC: 4016 AN: 5158

South Asian (SAS) AF: 0.783 AC: 3770 AN: 4816

European-Finnish (FIN) AF: 0.598 AC: 6297 AN: 10522

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37974 AN: 67884

Other (OTH) AF: 0.575 AC: 1215 AN: 2112

Alfa AF: 0.557 Hom.: 12304

Bravo AF: 0.516

Asia WGS AF: 0.755 AC: 2617 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.79
PhyloP100		0.65

Splicing

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

Other links and lift over

dbSNP: rs1422982; hg19: chr5-147420024;