19-55785540-T-C

Variant names:

• chr19-55785540-T-C
• rs199475863
• NM_001394894.2:c.*85A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394894.2(NLRP11):​c.*85A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 857,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00096 (0 hom.)
• Consequence: NLRP11 NM_001394894.2 3_prime_UTR
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.0330

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP11	NM_001394894.2	c.*85A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000589093.6	NP_001381823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP11	ENST00000589093	c.*85A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_001394894.2	ENSP00000466285.1

Frequencies

GnomAD3 genomes AF: 0.000797 AC: 99 AN: 124268 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000768

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000315

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000241

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000494

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.00115

GnomAD4 exome AF: 0.000961 AC: 704 AN: 732686 Hom.: 0 Cov.: 14 AF XY: 0.000920 AC XY: 346 AN XY: 376098

Gnomad4 AFR exome AF: 0.00266

Gnomad4 AMR exome AF: 0.000422

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000192

Gnomad4 SAS exome AF: 0.000178

Gnomad4 FIN exome AF: 0.000270

Gnomad4 NFE exome AF: 0.00114

Gnomad4 OTH exome AF: 0.000955

GnomAD4 genome AF: 0.000796 AC: 99 AN: 124372 Hom.: 0 Cov.: 31 AF XY: 0.000746 AC XY: 45 AN XY: 60308

Gnomad4 AFR AF: 0.000766

Gnomad4 AMR AF: 0.000314

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000241

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000494

Gnomad4 NFE AF: 0.00110

Gnomad4 OTH AF: 0.00114

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

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Human Evolutionary Genetics, Institut Pasteur

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.19

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: rs199475863; hg19: chr19-56296906;