19-55792440-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394894.2(NLRP11):c.2374T>G(p.Cys792Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 1,614,138 control chromosomes in the GnomAD database, including 316 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (156 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (160 hom.)
• Consequence: NLRP11 NM_001394894.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.621

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003106743).
• BP6: Variant 19-55792440-A-C is Benign according to our data. Variant chr19-55792440-A-C is described in ClinVar as [Benign]. Clinvar id is 710865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP11	NM_001394894.2	c.2374T>G	p.Cys792Gly	missense_variant	7/10	ENST00000589093.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP11	ENST00000589093.6	c.2374T>G	p.Cys792Gly	missense_variant	7/10	1	NM_001394894.2	P1

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3742 AN: 152212 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.00700 AC: 1759 AN: 251446 Hom.: 73 AF XY: 0.00486 AC XY: 661 AN XY: 135890

Gnomad AFR exome AF: 0.0920

Gnomad AMR exome AF: 0.00486

Gnomad ASJ exome AF: 0.00397

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00266 AC: 3895 AN: 1461808 Hom.: 160 Cov.: 31 AF XY: 0.00226 AC XY: 1647 AN XY: 727196

Gnomad4 AFR exome AF: 0.0889

Gnomad4 AMR exome AF: 0.00601

Gnomad4 ASJ exome AF: 0.00364

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.00646

GnomAD4 genome AF: 0.0246 AC: 3754 AN: 152330 Hom.: 156 Cov.: 32 AF XY: 0.0234 AC XY: 1741 AN XY: 74502

Gnomad4 AFR AF: 0.0836

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.00866 Hom.: 34

Bravo AF: 0.0288

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0810 AC: 357

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00835 AC: 1014

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	13
Dann	Benign	0.73
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.40	T;T;T
MetaRNN	Benign	0.0031	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.32	T
Sift4G	Benign	0.11	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.43
MVP		0.54
ClinPred		0.034	T
GERP RS		-0.11
Varity_R		0.11
gMVP		0.50

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: rs80143194; hg19: chr19-56303806;