rs2303068

Variant names:

• chr5-148101455-G-A
• rs2303068
• NM_006846.4:c.1302+19G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-148101455-G-A
• chr5-148101455-G-C
• chr5-148101455-G-T

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.1302+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,571,376 control chromosomes in the GnomAD database, including 205,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16469 hom., cov: 31)
  • Exomes 𝑓: 0.51 (189001 hom.)
• Consequence: SPINK5 NM_006846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.326
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-148101455-G-A is Benign according to our data. Variant chr5-148101455-G-A is described in ClinVar as Benign. ClinVar VariationId is 260044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.571 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.1302+19G>A		intron	N/A	NP_006837.2	Q9NQ38-1
	SPINK5	NM_001127698.2		c.1302+19G>A		intron	N/A	NP_001121170.1	Q9NQ38-3
	SPINK5	NM_001127699.2		c.1302+19G>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.1302+19G>A		intron	N/A	ENSP00000256084.7	Q9NQ38-1
	SPINK5	ENST00000359874.7	TSL:1	c.1302+19G>A		intron	N/A	ENSP00000352936.3	Q9NQ38-3
	SPINK5	ENST00000398454.5	TSL:1	c.1302+19G>A		intron	N/A	ENSP00000381472.1	Q9NQ38-2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67780 AN: 151470 Hom.: 16459 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.474

GnomAD2 exomes AF: 0.520 AC: 128745 AN: 247788 AF XY: 0.518

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.700

Gnomad ASJ exome AF: 0.462

Gnomad EAS exome AF: 0.473

Gnomad FIN exome AF: 0.550

Gnomad NFE exome AF: 0.519

Gnomad OTH exome AF: 0.524

GnomAD4 exome AF: 0.512 AC: 726380 AN: 1419788 Hom.: 189001 Cov.: 26 AF XY: 0.511 AC XY: 362251 AN XY: 708960

African (AFR) AF: 0.228 AC: 7476 AN: 32832

American (AMR) AF: 0.684 AC: 30468 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 11882 AN: 25810

East Asian (EAS) AF: 0.446 AC: 17583 AN: 39446

South Asian (SAS) AF: 0.488 AC: 41693 AN: 85404

European-Finnish (FIN) AF: 0.549 AC: 29281 AN: 53332

Middle Eastern (MID) AF: 0.507 AC: 2879 AN: 5680

European-Non Finnish (NFE) AF: 0.517 AC: 555617 AN: 1073708

Other (OTH) AF: 0.500 AC: 29501 AN: 59058

GnomAD4 genome AF: 0.447 AC: 67802 AN: 151588 Hom.: 16469 Cov.: 31 AF XY: 0.451 AC XY: 33388 AN XY: 73990

African (AFR) AF: 0.238 AC: 9827 AN: 41352

American (AMR) AF: 0.581 AC: 8834 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2424 AN: 5098

South Asian (SAS) AF: 0.491 AC: 2356 AN: 4796

European-Finnish (FIN) AF: 0.537 AC: 5622 AN: 10472

Middle Eastern (MID) AF: 0.490 AC: 141 AN: 288

European-Non Finnish (NFE) AF: 0.524 AC: 35556 AN: 67892

Other (OTH) AF: 0.477 AC: 1004 AN: 2106

Alfa AF: 0.472 Hom.: 4326

Bravo AF: 0.445

Asia WGS AF: 0.520 AC: 1803 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Ichthyosis linearis circumflexa (1)
-	-	1	Netherton syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.22
PhyloP100		-0.33
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: rs2303068; hg19: chr5-147481018; COSMIC: COSV56248208; COSMIC: COSV56248208;