rs2052532

Variant names:

• chr5-148116744-G-A
• rs2052532
• NM_006846.4:c.2112+278G>A

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.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
• 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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK5	NM_006846.4	MANE Select	c.2112+278G>A		intron	N/A	NP_006837.2	Q9NQ38-1
	SPINK5	NM_001127698.2		c.2112+278G>A		intron	N/A	NP_001121170.1	Q9NQ38-3
	SPINK5	NM_001127699.2		c.2112+278G>A		intron	N/A	NP_001121171.1	Q9NQ38-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK5	ENST00000256084.8	TSL:1 MANE Select	c.2112+278G>A		intron	N/A	ENSP00000256084.7	Q9NQ38-1
	SPINK5	ENST00000359874.7	TSL:1	c.2112+278G>A		intron	N/A	ENSP00000352936.3	Q9NQ38-3
	SPINK5	ENST00000398454.5	TSL:1	c.2112+278G>A		intron	N/A	ENSP00000381472.1	Q9NQ38-2

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

African (AFR) AF: 0.250 AC: 10347 AN: 41448

American (AMR) AF: 0.629 AC: 9620 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1836 AN: 3470

East Asian (EAS) AF: 0.471 AC: 2429 AN: 5152

South Asian (SAS) AF: 0.507 AC: 2433 AN: 4800

European-Finnish (FIN) AF: 0.636 AC: 6721 AN: 10562

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42809 AN: 67968

Other (OTH) AF: 0.525 AC: 1105 AN: 2104

Alfa AF: 0.547 Hom.: 3176

Bravo AF: 0.503

Asia WGS AF: 0.523 AC: 1815 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-0.56
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: rs2052532; hg19: chr5-147496307; COSMIC: COSV56250978;