dbSNP rs886054602: NLRP12:c.*430G>A (chr19-53793619-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001277129.1(NLRP12):c.*430G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000523 in 191,076 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

NLRP12
NM_001277129.1 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.373

Publications

0 publications found

Variant links:

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

NLRP12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BS2

High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277129.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NLRP12	NM_001277129.1		c.*430G>A	3_prime_UTR	Exon 9 of 9	NP_001264058.1	P59046-6
NLRP12	NM_144687.4	MANE Select	c.*430G>A	downstream_gene	N/A	NP_653288.1	P59046-1
NLRP12	NM_001277126.2		c.*430G>A	downstream_gene	N/A	NP_001264055.1	P59046-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NLRP12	ENST00000391773.8	TSL:1	c.*430G>A	3_prime_UTR	Exon 10 of 10	ENSP00000375653.1	P59046-7
NLRP12	ENST00000324134.11	TSL:1 MANE Select	c.*430G>A	downstream_gene	N/A	ENSP00000319377.6	P59046-1
NLRP12	ENST00000345770.9	TSL:1	c.*430G>A	downstream_gene	N/A	ENSP00000341428.5	A0A0C4DH17

Frequencies

GnomAD3 genomes

AF:

0.0000544

AC:

AN:

146930

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.000215

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000893

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000453

AC:

AN:

44146

Hom.:

Cov.:

AF XY:

0.0000419

AC XY:

AN XY:

23842

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1524

American (AMR)

AF:

0.00

AC:

AN:

3470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

734

East Asian (EAS)

AF:

0.00

AC:

AN:

2770

South Asian (SAS)

AF:

0.00

AC:

AN:

6456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

104

European-Non Finnish (NFE)

AF:

0.0000778

AC:

AN:

25708

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000544

AC:

AN:

146930

Hom.:

Cov.:

AF XY:

0.0000703

AC XY:

AN XY:

71106

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39718

American (AMR)

AF:

0.00

AC:

AN:

14438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

5004

South Asian (SAS)

AF:

0.00

AC:

AN:

4640

European-Finnish (FIN)

AF:

0.000215

AC:

AN:

9294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.0000893

AC:

AN:

67174

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000169

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial cold autoinflammatory syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

3.0

(source)

DANN

Benign

0.76

PhyloP100

0.37

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over