dbSNP rs302827: NLRP13:p.Leu957Leu (chr19-55898856-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_176810.2(NLRP13):c.2871G>A(p.Leu957Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,612,626 control chromosomes in the GnomAD database, including 63,269 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 4944 hom., cov: 32)

Exomes 𝑓: 0.28 ( 58325 hom. )

Consequence

NLRP13
NM_176810.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.299

Publications

19 publications found

Variant links:

Genes affected

NLRP13 (HGNC:22937): (NLR family pyrin domain containing 13) This gene encodes a member of the NACHT, leucine rich repeat, and PYD containing (NLRP) protein family. It has an N-terminal pyrin domain, followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region. NLRP proteins are implicated in the activation of proinflammatory caspases through multiprotein complexes called inflammasomes. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

NLRP13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=0.299 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP13	NM_176810.2 link	c.2871G>A	p.Leu957Leu	synonymous_variant	Exon 10 of 11	ENST00000342929.4	NP_789780.2
NLRP13	NM_001321057.1 link	c.2871G>A	p.Leu957Leu	synonymous_variant	Exon 10 of 12		NP_001307986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP13	ENST00000342929.4 link	c.2871G>A	p.Leu957Leu	synonymous_variant	Exon 10 of 11	1	NM_176810.2	ENSP00000343891.3		Q86W25
NLRP13	ENST00000588751.5 link	c.2871G>A	p.Leu957Leu	synonymous_variant	Exon 10 of 12	5		ENSP00000467899.1		A0A0C4DGQ4

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37951

AN:

151982

Hom.:

4942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.276

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.279

GnomAD2 exomes

AF:

0.274

AC:

68628

AN:

250212

AF XY:

0.276

show subpopulations

Gnomad AFR exome

AF:

0.165

Gnomad AMR exome

AF:

0.263

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.411

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.280

GnomAD4 exome

AF:

0.280

AC:

408580

AN:

1460526

Hom.:

58325

Cov.:

AF XY:

0.280

AC XY:

203406

AN XY:

726572

show subpopulations

African (AFR)

AF:

0.162

AC:

5414

AN:

33436

American (AMR)

AF:

0.263

AC:

11700

AN:

44510

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6331

AN:

26070

East Asian (EAS)

AF:

0.411

AC:

16297

AN:

39618

South Asian (SAS)

AF:

0.273

AC:

23502

AN:

86050

European-Finnish (FIN)

AF:

0.242

AC:

12903

AN:

53370

Middle Eastern (MID)

AF:

0.255

AC:

1472

AN:

5768

European-Non Finnish (NFE)

AF:

0.283

AC:

313986

AN:

1111362

Other (OTH)

AF:

0.281

AC:

16975

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

13880

27761

41641

55522

69402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.250

AC:

37969

AN:

152100

Hom.:

4944

Cov.:

AF XY:

0.249

AC XY:

18504

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.168

AC:

6983

AN:

41502

American (AMR)

AF:

0.276

AC:

4223

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

861

AN:

3472

East Asian (EAS)

AF:

0.411

AC:

2122

AN:

5160

South Asian (SAS)

AF:

0.286

AC:

1377

AN:

4820

European-Finnish (FIN)

AF:

0.237

AC:

2506

AN:

10584

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

19004

AN:

67966

Other (OTH)

AF:

0.284

AC:

599

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1477

2954

4432

5909

7386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.274

Hom.:

12566

Bravo

AF:

0.253

Asia WGS

AF:

0.344

AC:

1194

AN:

3478

EpiCase

AF:

0.282

EpiControl

AF:

0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.0

(source)

DANN

Benign

0.54

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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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rs302827

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over