5-148027816-G-A

Position:

• chr5-148027816-G-A

Variant summary

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

The ENST00000521206.5(SPINK5):​c.-183+2030G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,974 control chromosomes in the GnomAD database, including 5,724 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 0.18 (5724 hom., cov: 32)
• Consequence: SPINK5 ENST00000521206.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.148027816G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000521206.5	c.-183+2030G>A		intron_variant		4		ENSP00000430264.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27740 AN: 151856 Hom.: 5697 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0635

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.183 AC: 27828 AN: 151974 Hom.: 5724 Cov.: 32 AF XY: 0.181 AC XY: 13429 AN XY: 74286

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0633

Gnomad4 FIN AF: 0.0635

Gnomad4 NFE AF: 0.0423

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0870 Hom.: 758

Bravo AF: 0.202

Asia WGS AF: 0.114 AC: 398 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	2.2
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12332673; hg19: chr5-147407379;