rs199475863

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-55785540-T-A
• chr19-55785540-T-C
• chr19-55785540-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394894.2(NLRP11):​c.*85A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.000024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NLRP11 NM_001394894.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 0 publications found

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]

NLRP11 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394894.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP11	NM_001394894.2	MANE Select	c.*85A>T		3_prime_UTR	Exon 10 of 10	NP_001381823.1	P59045-1
	NLRP11	NM_145007.5		c.*85A>T		3_prime_UTR	Exon 12 of 12	NP_659444.2	P59045-1
	NLRP11	NM_001385451.2		c.*85A>T		3_prime_UTR	Exon 11 of 11	NP_001372380.1	P59045-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP11	ENST00000589093.6	TSL:1 MANE Select	c.*85A>T		3_prime_UTR	Exon 10 of 10	ENSP00000466285.1	P59045-1
	NLRP11	ENST00000592953.5	TSL:1	c.*85A>T		3_prime_UTR	Exon 9 of 9	ENSP00000468196.1	P59045-3
	NLRP11	ENST00000590409.5	TSL:1	n.*1001A>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000466582.1	K7EMN8

Frequencies

GnomAD3 genomes AF: 0.0000241 AC: 3 AN: 124260 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000278

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000348

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00128 AC: 936 AN: 730660 Hom.: 0 Cov.: 14 AF XY: 0.00115 AC XY: 431 AN XY: 375116

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000651 AC: 11 AN: 16888

American (AMR) AF: 0.000176 AC: 5 AN: 28444

Ashkenazi Jewish (ASJ) AF: 0.000828 AC: 11 AN: 13278

East Asian (EAS) AF: 0.000192 AC: 5 AN: 26056

South Asian (SAS) AF: 0.000178 AC: 10 AN: 56044

European-Finnish (FIN) AF: 0.000172 AC: 7 AN: 40768

Middle Eastern (MID) AF: 0.000758 AC: 2 AN: 2638

European-Non Finnish (NFE) AF: 0.00165 AC: 849 AN: 515202

Other (OTH) AF: 0.00115 AC: 36 AN: 31342

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000241 AC: 3 AN: 124364 Hom.: 0 Cov.: 31 AF XY: 0.0000332 AC XY: 2 AN XY: 60304

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32656

American (AMR) AF: 0.00 AC: 0 AN: 12734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2988

East Asian (EAS) AF: 0.00 AC: 0 AN: 4144

South Asian (SAS) AF: 0.000278 AC: 1 AN: 3602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000348 AC: 2 AN: 57392

Other (OTH) AF: 0.00 AC: 0 AN: 1754

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.22
PhyloP100		-0.033

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

Other links and lift over

dbSNP: rs199475863; hg19: chr19-56296906;