rs116411892

Variant names:

• chr19-53793846-A-G
• rs116411892
• NM_144687.4:c.*203T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_144687.4(NLRP12):​c.*203T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 649,460 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (23 hom., cov: 31)
  • Exomes 𝑓: 0.00097 (7 hom.)
• Consequence: NLRP12 NM_144687.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0760
• Publications: 0 publications found

Genes affected

NLRP12 (HGNC:22938): (NLR family pyrin domain containing 12) This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

NLRP12 Gene-Disease associations (from GenCC):

• familial cold autoinflammatory syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-53793846-A-G is Benign according to our data. Variant chr19-53793846-A-G is described in ClinVar as Benign. ClinVar VariationId is 329993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00793 (1206/152010) while in subpopulation AFR AF = 0.0276 (1145/41468). AF 95% confidence interval is 0.0263. There are 23 homozygotes in GnomAd4. There are 570 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1206 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144687.4. 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
	NLRP12	NM_144687.4	MANE Select	c.*203T>C		3_prime_UTR	Exon 10 of 10	NP_653288.1	P59046-1
	NLRP12	NM_001277126.2		c.*203T>C		3_prime_UTR	Exon 10 of 10	NP_001264055.1	P59046-7
	NLRP12	NM_001277129.1		c.*203T>C		3_prime_UTR	Exon 9 of 9	NP_001264058.1	P59046-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP12	ENST00000324134.11	TSL:1 MANE Select	c.*203T>C		3_prime_UTR	Exon 10 of 10	ENSP00000319377.6	P59046-1
	NLRP12	ENST00000391773.8	TSL:1	c.*203T>C		3_prime_UTR	Exon 10 of 10	ENSP00000375653.1	P59046-7
	NLRP12	ENST00000345770.9	TSL:1	c.*203T>C		3_prime_UTR	Exon 9 of 9	ENSP00000341428.5	A0A0C4DH17

Frequencies

GnomAD3 genomes AF: 0.00795 AC: 1207 AN: 151892 Hom.: 24 Cov.: 31

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00767

GnomAD4 exome AF: 0.000967 AC: 481 AN: 497450 Hom.: 7 Cov.: 3 AF XY: 0.000786 AC XY: 209 AN XY: 265856

African (AFR) AF: 0.0275 AC: 394 AN: 14332

American (AMR) AF: 0.000853 AC: 25 AN: 29304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16560

East Asian (EAS) AF: 0.00 AC: 0 AN: 31294

South Asian (SAS) AF: 0.0000370 AC: 2 AN: 54056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2170

European-Non Finnish (NFE) AF: 0.0000242 AC: 7 AN: 289496

Other (OTH) AF: 0.00190 AC: 53 AN: 27968

GnomAD4 genome AF: 0.00793 AC: 1206 AN: 152010 Hom.: 23 Cov.: 31 AF XY: 0.00767 AC XY: 570 AN XY: 74312

African (AFR) AF: 0.0276 AC: 1145 AN: 41468

American (AMR) AF: 0.00262 AC: 40 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67982

Other (OTH) AF: 0.00759 AC: 16 AN: 2108

Alfa AF: 0.00564 Hom.: 0

Bravo AF: 0.00876

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Familial cold autoinflammatory syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.37
PhyloP100		-0.076
Mutation Taster		=100/0	polymorphism

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: rs116411892; hg19: chr19-54297100;