19-55715799-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_176820.4(NLRP9):​c.2331-574T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,326 control chromosomes in the GnomAD database, including 929 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 0.10 ( 929 hom., cov: 32)

Consequence

NLRP9
NM_176820.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.177
Variant links:
Genes affected
NLRP9 (HGNC:22941): (NLR family pyrin domain containing 9) The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). This protein may play a regulatory role in the innate immune system as similar family members belong to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NLRP9NM_176820.4 linkc.2331-574T>C intron_variant Intron 5 of 8 ENST00000332836.7 NP_789790.2 Q7RTR0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NLRP9ENST00000332836.7 linkc.2331-574T>C intron_variant Intron 5 of 8 1 NM_176820.4 ENSP00000331857.2 Q7RTR0-1
NLRP9ENST00000590200.1 linkc.2331-574T>C intron_variant Intron 5 of 8 1 ENSP00000465253.1 Q7RTR0-2

Frequencies

GnomAD3 genomes
AF:
0.102
AC:
15597
AN:
152208
Hom.:
927
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0638
Gnomad AMI
AF:
0.182
Gnomad AMR
AF:
0.0823
Gnomad ASJ
AF:
0.155
Gnomad EAS
AF:
0.0517
Gnomad SAS
AF:
0.118
Gnomad FIN
AF:
0.0460
Gnomad MID
AF:
0.196
Gnomad NFE
AF:
0.138
Gnomad OTH
AF:
0.109
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.102
AC:
15606
AN:
152326
Hom.:
929
Cov.:
32
AF XY:
0.0977
AC XY:
7278
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0640
Gnomad4 AMR
AF:
0.0821
Gnomad4 ASJ
AF:
0.155
Gnomad4 EAS
AF:
0.0518
Gnomad4 SAS
AF:
0.118
Gnomad4 FIN
AF:
0.0460
Gnomad4 NFE
AF:
0.138
Gnomad4 OTH
AF:
0.108
Alfa
AF:
0.130
Hom.:
1834
Bravo
AF:
0.102
Asia WGS
AF:
0.0590
AC:
206
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
6.7
DANN
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs11882068; hg19: chr19-56227165; API