chr19-53804068-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_144687.4(NLRP12):c.2469C>T(p.Leu823Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,613,480 control chromosomes in the GnomAD database, including 253,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L823L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.47 ( 18607 hom., cov: 31)

Exomes 𝑓: 0.56 ( 234809 hom. )

Consequence

NLRP12
NM_144687.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.00600

Publications

18 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, Laboratory for Molecular Medicine

NLRP12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-53804068-G-A is Benign according to our data. Variant chr19-53804068-G-A is described in ClinVar as Benign. ClinVar VariationId is 262531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.006 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP12	NM_144687.4 link	c.2469C>T	p.Leu823Leu	synonymous_variant	Exon 6 of 10	ENST00000324134.11	NP_653288.1	P59046-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NLRP12	ENST00000324134.11 link	c.2469C>T	p.Leu823Leu	synonymous_variant	Exon 6 of 10	1	NM_144687.4	ENSP00000319377.6	P59046-1
NLRP12	ENST00000345770.9 link	c.2472C>T	p.Leu824Leu	synonymous_variant	Exon 6 of 9	1		ENSP00000341428.5	A0A0C4DH17
NLRP12	ENST00000391772.1 link	c.2472C>T	p.Leu824Leu	synonymous_variant	Exon 6 of 7	1		ENSP00000375652.1	A0A0C4DFY3

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70669

AN:

151808

Hom.:

18602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.660

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.584

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.595

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.576

Gnomad OTH

AF:

0.508

GnomAD2 exomes

AF:

0.530

AC:

133138

AN:

251008

AF XY:

0.531

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.558

Gnomad ASJ exome

AF:

0.584

Gnomad EAS exome

AF:

0.576

Gnomad FIN exome

AF:

0.591

Gnomad NFE exome

AF:

0.579

Gnomad OTH exome

AF:

0.546

GnomAD4 exome

AF:

0.561

AC:

820227

AN:

1461552

Hom.:

234809

Cov.:

AF XY:

0.558

AC XY:

405557

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.183

AC:

6132

AN:

33478

American (AMR)

AF:

0.557

AC:

24903

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.582

AC:

15213

AN:

26134

East Asian (EAS)

AF:

0.525

AC:

20840

AN:

39688

South Asian (SAS)

AF:

0.410

AC:

35354

AN:

86250

European-Finnish (FIN)

AF:

0.589

AC:

31460

AN:

53380

Middle Eastern (MID)

AF:

0.507

AC:

2925

AN:

5768

European-Non Finnish (NFE)

AF:

0.585

AC:

650736

AN:

1111772

Other (OTH)

AF:

0.541

AC:

32664

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20596

41192

61788

82384

102980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17784

35568

53352

71136

88920

<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:

0.465

AC:

70680

AN:

151928

Hom.:

18607

Cov.:

AF XY:

0.469

AC XY:

34777

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.199

AC:

8240

AN:

41450

American (AMR)

AF:

0.544

AC:

8283

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.584

AC:

2025

AN:

3466

East Asian (EAS)

AF:

0.574

AC:

2954

AN:

5148

South Asian (SAS)

AF:

0.409

AC:

1967

AN:

4808

European-Finnish (FIN)

AF:

0.595

AC:

6273

AN:

10544

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.576

AC:

39146

AN:

67968

Other (OTH)

AF:

0.505

AC:

1066

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1728

3456

5183

6911

8639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.539

Hom.:

4657

EpiCase

AF:

0.563

EpiControl

AF:

0.570

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 81% of patients studied by a panel of primary immunodeficiencies. Number of patients: 78. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial cold autoinflammatory syndrome 2

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Familial cold autoinflammatory syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.1

(source)

DANN

Benign

0.56

PhyloP100

0.0060

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over