rs2052532

Positions:

• chr5-148116744-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006846.4(SPINK5):​c.2112+278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,996 control chromosomes in the GnomAD database, including 22,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (22178 hom., cov: 32)
• Consequence: SPINK5 NM_006846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.558

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-148116744-G-A is Benign according to our data. Variant chr5-148116744-G-A is described in ClinVar as [Benign]. Clinvar id is 667631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.2112+278G>A		intron_variant		ENST00000256084.8	NP_006837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8	c.2112+278G>A		intron_variant		1	NM_006846.4	ENSP00000256084.7

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77968 AN: 151880 Hom.: 22166 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.513 AC: 77991 AN: 151996 Hom.: 22178 Cov.: 32 AF XY: 0.514 AC XY: 38223 AN XY: 74300

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.525

Alfa AF: 0.559 Hom.: 3148

Bravo AF: 0.503

Asia WGS AF: 0.523 AC: 1815 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2052532; hg19: chr5-147496307; COSMIC: COSV56250978;