rs299175

Positions:

• chr19-55802162-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394894.2(NLRP11):​c.2004-423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,934 control chromosomes in the GnomAD database, including 13,943 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 0.43 (13943 hom., cov: 32)
• Consequence: NLRP11 NM_001394894.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

Genes affected

NLRP11 (HGNC:22945): (NLR family pyrin domain containing 11) This gene is a member of the the NOD-like receptor protein (NLRP) gene family and encodes a protein with an N-terminal pyrin death (PYD) domain and nucleoside triphosphate hydrolase (NACHT) domain and a C-terminal leucine-rich repeats (LRR) region. This gene has been shown to regulate caspases in the proinflammatory signal transduction pathway and, based on studies of other members of the NLRP gene family with similar domain structure, is predicted to form part of the multiprotein inflammasome complex. Alternative splicing produces multiple transcript variants encoding distince isoforms. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP11	NM_001394894.2	c.2004-423C>T		intron_variant		ENST00000589093.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP11	ENST00000589093.6	c.2004-423C>T		intron_variant		1	NM_001394894.2	P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64909 AN: 151814 Hom.: 13925 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.428 AC: 64975 AN: 151934 Hom.: 13943 Cov.: 32 AF XY: 0.426 AC XY: 31623 AN XY: 74246

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.446

Alfa AF: 0.447 Hom.: 35282

Bravo AF: 0.431

Asia WGS AF: 0.404 AC: 1405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs299175; hg19: chr19-56313528;