Genetic Variant NLRP12:c.*402G>A (chr19-53793647-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.*402G>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 0.0000604 in 149,034 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 0.000060 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000062 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NLRP12
NM_001277129.1 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.205

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=-0.96).

BS2

High AC in GnomAd4 at 9 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.*402G>A	3_prime_UTR	Exon 9 of 9	NP_001264058.1	P59046-6
NLRP12	NM_144687.4	MANE Select	c.*402G>A	downstream_gene	N/A	NP_653288.1	P59046-1
NLRP12	NM_001277126.2		c.*402G>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.*402G>A	3_prime_UTR	Exon 10 of 10	ENSP00000375653.1	P59046-7
NLRP12	ENST00000324134.11	TSL:1 MANE Select	c.*402G>A	downstream_gene	N/A	ENSP00000319377.6	P59046-1
NLRP12	ENST00000345770.9	TSL:1	c.*402G>A	downstream_gene	N/A	ENSP00000341428.5	A0A0C4DH17

Frequencies

GnomAD3 genomes

AF:

0.0000604

AC:

AN:

148928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000679

Gnomad ASJ

AF:

0.000291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00327

Gnomad NFE

AF:

0.0000593

Gnomad OTH

AF:

0.000489

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000617

AC:

AN:

113466

Hom.:

Cov.:

AF XY:

0.0000987

AC XY:

AN XY:

60804

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

4150

American (AMR)

AF:

0.000165

AC:

AN:

6060

Ashkenazi Jewish (ASJ)

AF:

0.000386

AC:

AN:

2588

East Asian (EAS)

AF:

0.00

AC:

AN:

5988

South Asian (SAS)

AF:

0.000109

AC:

AN:

18288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

386

European-Non Finnish (NFE)

AF:

0.0000454

AC:

AN:

66036

Other (OTH)

AF:

0.00

AC:

AN:

5786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000604

AC:

AN:

149034

Hom.:

Cov.:

AF XY:

0.0000690

AC XY:

AN XY:

72508

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40446

American (AMR)

AF:

0.0000678

AC:

AN:

14742

Ashkenazi Jewish (ASJ)

AF:

0.000291

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

5052

South Asian (SAS)

AF:

0.000213

AC:

AN:

4700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9920

Middle Eastern (MID)

AF:

0.00352

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000593

AC:

AN:

67484

Other (OTH)

AF:

0.000484

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

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:

0.0000843

Hom.:

ClinVar

ClinVar submissions

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

-0.96

CADD

Benign

3.3

(source)

DANN

Benign

0.40

PhyloP100

0.20

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over