19-55715799-A-G

Variant names:

• chr19-55715799-A-G
• rs11882068
• NM_176820.4:c.2331-574T>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

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]

ACMG classification

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
NLRP9	NM_176820.4	c.2331-574T>C		intron_variant	Intron 5 of 8	ENST00000332836.7	NP_789790.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP9	ENST00000332836.7	c.2331-574T>C		intron_variant	Intron 5 of 8	1	NM_176820.4	ENSP00000331857.2
NLRP9	ENST00000590200.1	c.2331-574T>C		intron_variant	Intron 5 of 8	1		ENSP00000465253.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15597 AN: 152208 Hom.: 927 Cov.: 32

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

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

Other links and lift over

dbSNP: rs11882068; hg19: chr19-56227165;