5-148033937-T-G

Variant names:

• chr5-148033937-T-G
• rs11948836
• ENST00000521206.5:c.-183+8151T>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+8151T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,170 control chromosomes in the GnomAD database, including 2,806 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 0.14 (2806 hom., cov: 32)
• Consequence: SPINK5 ENST00000521206.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000521206.5	c.-183+8151T>G		intron_variant	Intron 1 of 4	4		ENSP00000430264.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20689 AN: 152052 Hom.: 2785 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.0620

Gnomad FIN AF: 0.0634

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0932

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

GnomAD4 genome AF: 0.136 AC: 20768 AN: 152170 Hom.: 2806 Cov.: 32 AF XY: 0.136 AC XY: 10090 AN XY: 74396

African (AFR) AF: 0.348 AC: 14409 AN: 41462

American (AMR) AF: 0.0956 AC: 1462 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3472

East Asian (EAS) AF: 0.130 AC: 671 AN: 5170

South Asian (SAS) AF: 0.0626 AC: 302 AN: 4822

European-Finnish (FIN) AF: 0.0634 AC: 673 AN: 10608

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0421 AC: 2862 AN: 68024

Other (OTH) AF: 0.0922 AC: 195 AN: 2114

Alfa AF: 0.0721 Hom.: 2979

Bravo AF: 0.148

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.75
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs11948836; hg19: chr5-147413500;