5-148106796-C-T

Variant names:

• chr5-148106796-C-T
• rs1422987
• NM_006846.4:c.1480-241C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006846.4(SPINK5):​c.1480-241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,956 control chromosomes in the GnomAD database, including 10,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (10255 hom., cov: 32)
• Consequence: SPINK5 NM_006846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.76
• Publications: 7 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]

FBXO38-DT (HGNC:55589): (FBXO38 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-148106796-C-T is Benign according to our data. Variant chr5-148106796-C-T is described in ClinVar as Benign. ClinVar VariationId is 677118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006846.4. 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
	SPINK5	NM_006846.4	MANE Select	c.1480-241C>T		intron	N/A	NP_006837.2
	SPINK5	NM_001127698.2		c.1480-241C>T		intron	N/A	NP_001121170.1
	SPINK5	NM_001127699.2		c.1480-241C>T		intron	N/A	NP_001121171.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK5	ENST00000256084.8	TSL:1 MANE Select	c.1480-241C>T		intron	N/A	ENSP00000256084.7
	SPINK5	ENST00000359874.7	TSL:1	c.1480-241C>T		intron	N/A	ENSP00000352936.3
	SPINK5	ENST00000398454.5	TSL:1	c.1480-241C>T		intron	N/A	ENSP00000381472.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43972 AN: 151838 Hom.: 10217 Cov.: 32

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.290 AC: 44057 AN: 151956 Hom.: 10255 Cov.: 32 AF XY: 0.292 AC XY: 21722 AN XY: 74278

African (AFR) AF: 0.635 AC: 26284 AN: 41366

American (AMR) AF: 0.191 AC: 2921 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2273 AN: 5158

South Asian (SAS) AF: 0.362 AC: 1744 AN: 4822

European-Finnish (FIN) AF: 0.148 AC: 1564 AN: 10574

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7843 AN: 67994

Other (OTH) AF: 0.260 AC: 549 AN: 2110

Alfa AF: 0.223 Hom.: 2189

Bravo AF: 0.305

Asia WGS AF: 0.361 AC: 1257 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.76
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1422987; hg19: chr5-147486359;