chr5-148088671-C-G

Variant names:

• chr5-148088671-C-G
• rs7711953
• NM_006846.4:c.474+66C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006846.4(SPINK5):​c.474+66C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,488,210 control chromosomes in the GnomAD database, including 194,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17128 hom., cov: 30)
  • Exomes 𝑓: 0.51 (177859 hom.)
• Consequence: SPINK5 NM_006846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75
• Publications: 6 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)

LOC124901185 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-148088671-C-G is Benign according to our data. Variant chr5-148088671-C-G is described in ClinVar as [Benign]. Clinvar id is 1222588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK5	NM_006846.4	c.474+66C>G		intron_variant	Intron 6 of 32	ENST00000256084.8	NP_006837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK5	ENST00000256084.8	c.474+66C>G		intron_variant	Intron 6 of 32	1	NM_006846.4	ENSP00000256084.7

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70426 AN: 151158 Hom.: 17125 Cov.: 30

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.499

GnomAD4 exome AF: 0.513 AC: 686063 AN: 1336934 Hom.: 177859 AF XY: 0.512 AC XY: 343305 AN XY: 670944

African (AFR) AF: 0.307 AC: 9387 AN: 30620

American (AMR) AF: 0.687 AC: 29835 AN: 43434

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 12630 AN: 25128

East Asian (EAS) AF: 0.477 AC: 18500 AN: 38780

South Asian (SAS) AF: 0.493 AC: 40716 AN: 82532

European-Finnish (FIN) AF: 0.545 AC: 28739 AN: 52746

Middle Eastern (MID) AF: 0.536 AC: 2959 AN: 5518

European-Non Finnish (NFE) AF: 0.514 AC: 514674 AN: 1001968

Other (OTH) AF: 0.509 AC: 28623 AN: 56208

GnomAD4 genome AF: 0.466 AC: 70438 AN: 151276 Hom.: 17128 Cov.: 30 AF XY: 0.471 AC XY: 34769 AN XY: 73874

African (AFR) AF: 0.310 AC: 12806 AN: 41270

American (AMR) AF: 0.594 AC: 9005 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1707 AN: 3462

East Asian (EAS) AF: 0.494 AC: 2513 AN: 5082

South Asian (SAS) AF: 0.498 AC: 2382 AN: 4782

European-Finnish (FIN) AF: 0.534 AC: 5623 AN: 10536

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34739 AN: 67676

Other (OTH) AF: 0.499 AC: 1048 AN: 2102

Alfa AF: 0.462 Hom.: 2032

Bravo AF: 0.466

Asia WGS AF: 0.531 AC: 1842 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

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 89% of patients studied by a panel of primary immunodeficiencies. Number of patients: 78. Only high quality variants are reported. -

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	0.29
DANN	Benign	0.69
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: rs7711953; hg19: chr5-147468234; COSMIC: COSV56261181; COSMIC: COSV56261181;