Variant 19-53807707-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144687.4(NLRP12):c.2073-42C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 1,610,424 control chromosomes in the GnomAD database, including 601,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 52896 hom., cov: 32)

Exomes 𝑓: 0.87 ( 548914 hom. )

Consequence

NLRP12
NM_144687.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.773

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 links:

NLRP12 (HGNC:):

NLRP12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-53807707-G-C is Benign according to our data. Variant chr19-53807707-G-C is described in ClinVar as [Benign]. Clinvar id is 1230124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP12	NM_144687.4 linkuse as main transcript	c.2073-42C>G		intron_variant		ENST00000324134.11	NP_653288.1	P59046-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
NLRP12	ENST00000324134.11 linkuse as main transcript	c.2073-42C>G	intron_variant	1	NM_144687.4	ENSP00000319377.6	P59046-1
NLRP12	ENST00000345770.9 linkuse as main transcript	c.2073-39C>G	intron_variant	1		ENSP00000341428.5	A0A0C4DH17
NLRP12	ENST00000391772.1 linkuse as main transcript	c.2073-39C>G	intron_variant	1		ENSP00000375652.1	A0A0C4DFY3

Frequencies

GnomAD3 genomes

AF:

0.831

AC:

126374

AN:

152012

Hom.:

52868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.737

Gnomad AMI

AF:

0.831

Gnomad AMR

AF:

0.856

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.750

Gnomad SAS

AF:

0.801

Gnomad FIN

AF:

0.892

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.881

Gnomad OTH

AF:

0.837

GnomAD3 exomes

AF:

0.844

AC:

211813

AN:

250824

Hom.:

89835

AF XY:

0.846

AC XY:

114686

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.736

Gnomad AMR exome

AF:

0.836

Gnomad ASJ exome

AF:

0.852

Gnomad EAS exome

AF:

0.749

Gnomad SAS exome

AF:

0.796

Gnomad FIN exome

AF:

0.886

Gnomad NFE exome

AF:

0.882

Gnomad OTH exome

AF:

0.855

GnomAD4 exome

AF:

0.866

AC:

1263240

AN:

1458292

Hom.:

548914

Cov.:

AF XY:

0.864

AC XY:

627316

AN XY:

725656

show subpopulations

Gnomad4 AFR exome

AF:

0.727

Gnomad4 AMR exome

AF:

0.838

Gnomad4 ASJ exome

AF:

0.854

Gnomad4 EAS exome

AF:

0.691

Gnomad4 SAS exome

AF:

0.798

Gnomad4 FIN exome

AF:

0.886

Gnomad4 NFE exome

AF:

0.883

Gnomad4 OTH exome

AF:

0.855

GnomAD4 genome

AF:

0.831

AC:

126457

AN:

152132

Hom.:

52896

Cov.:

AF XY:

0.832

AC XY:

61899

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.737

Gnomad4 AMR

AF:

0.857

Gnomad4 ASJ

AF:

0.855

Gnomad4 EAS

AF:

0.750

Gnomad4 SAS

AF:

0.802

Gnomad4 FIN

AF:

0.892

Gnomad4 NFE

AF:

0.881

Gnomad4 OTH

AF:

0.835

Alfa

AF:

0.839

Hom.:

5548

Bravo

AF:

0.824

Asia WGS

AF:

0.783

AC:

2721

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 90% of patients studied by a panel of primary immunodeficiencies. Number of patients: 86. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.066

DANN

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over