rs3815740

Variant names:

• chr5-148111630-A-G
• rs3815740
• NM_006846.4:c.1693-138A>G

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.1693-138A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,263,794 control chromosomes in the GnomAD database, including 11,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2435 hom., cov: 32)
  • Exomes 𝑓: 0.10 (9196 hom.)
• Consequence: SPINK5 NM_006846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0290
• Publications: 5 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=-0.87).
• BP6: Variant 5-148111630-A-G is Benign according to our data. Variant chr5-148111630-A-G is described in ClinVar as Benign. ClinVar VariationId is 1270948.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.1693-138A>G		intron_variant	Intron 18 of 32	ENST00000256084.8	NP_006837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8	c.1693-138A>G		intron_variant	Intron 18 of 32	1	NM_006846.4	ENSP00000256084.7

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23210 AN: 152050 Hom.: 2421 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.0901

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.104 AC: 115515 AN: 1111626 Hom.: 9196 AF XY: 0.111 AC XY: 62450 AN XY: 563730

African (AFR) AF: 0.265 AC: 6772 AN: 25554

American (AMR) AF: 0.0754 AC: 2854 AN: 37860

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4400 AN: 23038

East Asian (EAS) AF: 0.297 AC: 10320 AN: 34778

South Asian (SAS) AF: 0.285 AC: 21112 AN: 74074

European-Finnish (FIN) AF: 0.0876 AC: 3588 AN: 40978

Middle Eastern (MID) AF: 0.184 AC: 701 AN: 3814

European-Non Finnish (NFE) AF: 0.0727 AC: 59835 AN: 823192

Other (OTH) AF: 0.123 AC: 5933 AN: 48338

GnomAD4 genome AF: 0.153 AC: 23251 AN: 152168 Hom.: 2435 Cov.: 32 AF XY: 0.155 AC XY: 11557 AN XY: 74410

African (AFR) AF: 0.267 AC: 11079 AN: 41474

American (AMR) AF: 0.0977 AC: 1494 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3472

East Asian (EAS) AF: 0.322 AC: 1664 AN: 5170

South Asian (SAS) AF: 0.299 AC: 1438 AN: 4816

European-Finnish (FIN) AF: 0.0901 AC: 956 AN: 10612

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.0810 AC: 5509 AN: 68014

Other (OTH) AF: 0.165 AC: 349 AN: 2114

Alfa AF: 0.123 Hom.: 225

Bravo AF: 0.155

Asia WGS AF: 0.259 AC: 899 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		-0.029
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: rs3815740; hg19: chr5-147491193;