chr5-148095925-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006846.4(SPINK5):c.882+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,592,966 control chromosomes in the GnomAD database, including 207,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17090 hom., cov: 31)

Exomes 𝑓: 0.51 ( 190513 hom. )

Consequence

SPINK5
NM_006846.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0110

Publications

6 publications found

Variant links:

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 links:

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

FBXO38-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-148095925-A-G is Benign according to our data. Variant chr5-148095925-A-G is described in ClinVar as Benign. ClinVar VariationId is 260056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK5	NM_006846.4 link	c.882+20A>G		intron_variant	Intron 10 of 32	ENST00000256084.8	NP_006837.2	Q9NQ38-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8 link	c.882+20A>G		intron_variant	Intron 10 of 32	1	NM_006846.4	ENSP00000256084.7		Q9NQ38-1

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70330

AN:

151610

Hom.:

17084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.506

Gnomad AMR

AF:

0.589

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.489

GnomAD2 exomes

AF:

0.521

AC:

129019

AN:

247402

AF XY:

0.518

show subpopulations

Gnomad AFR exome

AF:

0.310

Gnomad AMR exome

AF:

0.703

Gnomad ASJ exome

AF:

0.458

Gnomad EAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.546

Gnomad NFE exome

AF:

0.513

Gnomad OTH exome

AF:

0.523

GnomAD4 exome

AF:

0.510

AC:

735732

AN:

1441238

Hom.:

190513

Cov.:

AF XY:

0.509

AC XY:

365742

AN XY:

718252

show subpopulations

African (AFR)

AF:

0.299

AC:

9861

AN:

33008

American (AMR)

AF:

0.687

AC:

30559

AN:

44452

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

11820

AN:

25902

East Asian (EAS)

AF:

0.450

AC:

17777

AN:

39508

South Asian (SAS)

AF:

0.486

AC:

41713

AN:

85800

European-Finnish (FIN)

AF:

0.545

AC:

29007

AN:

53240

Middle Eastern (MID)

AF:

0.511

AC:

2887

AN:

5652

European-Non Finnish (NFE)

AF:

0.514

AC:

562205

AN:

1094140

Other (OTH)

AF:

0.502

AC:

29903

AN:

59536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

15578

31156

46734

62312

77890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16114

32228

48342

64456

80570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.464

AC:

70350

AN:

151728

Hom.:

17090

Cov.:

AF XY:

0.467

AC XY:

34635

AN XY:

74128

show subpopulations

African (AFR)

AF:

0.307

AC:

12701

AN:

41402

American (AMR)

AF:

0.590

AC:

8970

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

1558

AN:

3468

East Asian (EAS)

AF:

0.473

AC:

2417

AN:

5110

South Asian (SAS)

AF:

0.490

AC:

2363

AN:

4820

European-Finnish (FIN)

AF:

0.533

AC:

5622

AN:

10548

Middle Eastern (MID)

AF:

0.497

AC:

145

AN:

292

European-Non Finnish (NFE)

AF:

0.517

AC:

35086

AN:

67872

Other (OTH)

AF:

0.490

AC:

1029

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1871

3742

5613

7484

9355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.475

Hom.:

6114

Bravo

AF:

0.466

Asia WGS

AF:

0.520

AC:

1804

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 88% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -

Ichthyosis linearis circumflexa

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Netherton syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.5

(source)

DANN

Benign

0.38

PhyloP100

-0.011

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over