rs1422982

chr5-148040461-A-Gchr5-148040461-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINK5	ENST00000521206.5	c.-183+14675A>G		intron_variant		4

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.575

Alfa AF: 0.561 Hom.: 11071

Bravo AF: 0.516

Asia WGS AF: 0.755 AC: 2617 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.0
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1422982; hg19: chr5-147420024;