NM_144687.4:c.-12C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144687.4(NLRP12):c.-12C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,612,406 control chromosomes in the GnomAD database, including 233,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17175 hom., cov: 31)

Exomes 𝑓: 0.54 ( 216202 hom. )

Consequence

NLRP12
NM_144687.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.624

Publications

20 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 -20 ACMG points.

BP4

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

BP6

Variant 19-53824186-G-A is Benign according to our data. Variant chr19-53824186-G-A is described in ClinVar as Benign. ClinVar VariationId is 262527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP12	NM_144687.4 link	c.-12C>T		5_prime_UTR_variant	Exon 1 of 10	ENST00000324134.11	NP_653288.1	P59046-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NLRP12	ENST00000324134.11 link	c.-12C>T	5_prime_UTR_variant	Exon 1 of 10	1	NM_144687.4	ENSP00000319377.6	P59046-1
NLRP12	ENST00000345770.9 link	c.-12C>T	5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000341428.5	A0A0C4DH17
NLRP12	ENST00000391772.1 link	c.-12C>T	5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000375652.1	A0A0C4DFY3

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

68893

AN:

151838

Hom.:

17171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.475

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.646

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.509

GnomAD2 exomes

AF:

0.509

AC:

127254

AN:

249930

AF XY:

0.515

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.643

Gnomad EAS exome

AF:

0.540

Gnomad FIN exome

AF:

0.571

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.531

GnomAD4 exome

AF:

0.540

AC:

788583

AN:

1460450

Hom.:

216202

Cov.:

AF XY:

0.539

AC XY:

391424

AN XY:

726542

show subpopulations

African (AFR)

AF:

0.216

AC:

7231

AN:

33462

American (AMR)

AF:

0.470

AC:

20985

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.642

AC:

16767

AN:

26128

East Asian (EAS)

AF:

0.587

AC:

23318

AN:

39694

South Asian (SAS)

AF:

0.445

AC:

38378

AN:

86218

European-Finnish (FIN)

AF:

0.569

AC:

30037

AN:

52760

Middle Eastern (MID)

AF:

0.522

AC:

3003

AN:

5756

European-Non Finnish (NFE)

AF:

0.555

AC:

617284

AN:

1111374

Other (OTH)

AF:

0.523

AC:

31580

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

17812

35624

53435

71247

89059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17208

34416

51624

68832

86040

<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:

0.454

AC:

68914

AN:

151956

Hom.:

17175

Cov.:

AF XY:

0.456

AC XY:

33878

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.231

AC:

9570

AN:

41454

American (AMR)

AF:

0.477

AC:

7273

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

2242

AN:

3472

East Asian (EAS)

AF:

0.554

AC:

2849

AN:

5146

South Asian (SAS)

AF:

0.430

AC:

2071

AN:

4814

European-Finnish (FIN)

AF:

0.563

AC:

5953

AN:

10566

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.549

AC:

37336

AN:

67950

Other (OTH)

AF:

0.503

AC:

1061

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1797

3594

5391

7188

8985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.530

Hom.:

13436

Bravo

AF:

0.440

Asia WGS

AF:

0.436

AC:

1517

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial cold autoinflammatory syndrome 2

Benign:4

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 70. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

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

5.9

(source)

DANN

Benign

0.85

PhyloP100

0.62

PromoterAI

0.012

Neutral

(source)

Mutation Taster

=300/0

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

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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