rs104895502

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM5

The ENST00000592784.6(NLRP7):​c.2078G>T​(p.Arg693Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R693P) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NLRP7
ENST00000592784.6 missense

Scores

7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300
Variant links:
Genes affected
NLRP7 (HGNC:22947): (NLR family pyrin domain containing 7) 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. This gene may act as a feedback regulator of caspase-1-dependent interleukin 1-beta secretion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1
In a repeat LRR 2 (size 23) in uniprot entity NALP7_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in ENST00000592784.6
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr19-54938095-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 1587.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NLRP7NM_001127255.2 linkuse as main transcriptc.2078G>T p.Arg693Leu missense_variant 5/11 ENST00000592784.6 NP_001120727.1
NLRP7NM_001405531.1 linkuse as main transcriptc.2078G>T p.Arg693Leu missense_variant 7/13 NP_001392460.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NLRP7ENST00000592784.6 linkuse as main transcriptc.2078G>T p.Arg693Leu missense_variant 5/111 NM_001127255.2 ENSP00000468706 P2Q8WX94-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461870
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Benign
0.0090
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.18
T;.;T;.;.
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.38
N
M_CAP
Benign
0.0051
T
MetaRNN
Uncertain
0.50
T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.5
M;.;M;M;M
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-4.1
D;.;.;.;.
REVEL
Benign
0.21
Sift
Uncertain
0.013
D;.;.;.;.
Sift4G
Uncertain
0.0090
D;D;D;D;D
Polyphen
0.13
B;B;B;.;.
Vest4
0.58
MVP
0.46
MPC
0.37
ClinPred
0.70
D
GERP RS
1.1
Varity_R
0.30
gMVP
0.37

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs104895502; hg19: chr19-55449463; API