rs302827

Variant names:

• chr19-55898856-C-T
• rs302827
• NM_176810.2:c.2871G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 19 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176810.2. 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
	NLRP13	NM_176810.2	MANE Select	c.2871G>A	p.Leu957Leu	synonymous	Exon 10 of 11	NP_789780.2	Q86W25
	NLRP13	NM_001321057.1		c.2871G>A	p.Leu957Leu	synonymous	Exon 10 of 12	NP_001307986.1	Q86W25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP13	ENST00000342929.4	TSL:1 MANE Select	c.2871G>A	p.Leu957Leu	synonymous	Exon 10 of 11	ENSP00000343891.3	Q86W25
	NLRP13	ENST00000850974.1		c.3033G>A	p.Leu1011Leu	synonymous	Exon 11 of 13	ENSP00000521056.1
	NLRP13	ENST00000588751.5	TSL:5	c.2871G>A	p.Leu957Leu	synonymous	Exon 10 of 12	ENSP00000467899.1	A0A0C4DGQ4

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37951 AN: 151982 Hom.: 4942 Cov.: 32

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

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.: 34 AF XY: 0.280 AC XY: 203406 AN XY: 726572

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

GnomAD4 genome AF: 0.250 AC: 37969 AN: 152100 Hom.: 4944 Cov.: 32 AF XY: 0.249 AC XY: 18504 AN XY: 74344

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: 87 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19004 AN: 67966

Other (OTH) AF: 0.284 AC: 599 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.54
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs302827; hg19: chr19-56410222; COSMIC: COSV61621081;