Variant rs455060 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001199138.2(NLRC4):c.1824C>T(p.Ala608Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,613,862 control chromosomes in the GnomAD database, including 302,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30064 hom., cov: 33)

Exomes 𝑓: 0.61 ( 272349 hom. )

Consequence

NLRC4
NM_001199138.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -0.839

Variant links:

Genes affected

NLRC4 (HGNC:16412): (NLR family CARD domain containing 4) This gene encodes a member of the caspase recruitment domain-containing NLR family. Family members play essential roles in innate immune response to a wide range of pathogenic organisms, tissue damage and other cellular stresses. Mutations in this gene result in autoinflammation with infantile enterocolitis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

NLRC4 links:

ENSG00000289727 (HGNC:):

ENSG00000289727 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-32250040-G-A is Benign according to our data. Variant chr2-32250040-G-A is described in ClinVar as [Benign]. Clinvar id is 403236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-32250040-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.839 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC4	NM_001199138.2 link	c.1824C>T	p.Ala608Ala	synonymous_variant	4/9	ENST00000402280.6	NP_001186067.1	Q9NPP4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRC4	ENST00000402280.6 link	c.1824C>T	p.Ala608Ala	synonymous_variant	4/9	1	NM_001199138.2	ENSP00000385428.1		Q9NPP4-1

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

95145

AN:

151992

Hom.:

30035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.649

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.647

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.611

Gnomad OTH

AF:

0.631

GnomAD3 exomes

AF:

0.592

AC:

148955

AN:

251420

Hom.:

44939

AF XY:

0.586

AC XY:

79643

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.651

Gnomad ASJ exome

AF:

0.524

Gnomad EAS exome

AF:

0.430

Gnomad SAS exome

AF:

0.517

Gnomad FIN exome

AF:

0.646

Gnomad NFE exome

AF:

0.603

Gnomad OTH exome

AF:

0.595

GnomAD4 exome

AF:

0.608

AC:

889327

AN:

1461754

Hom.:

272349

Cov.:

AF XY:

0.604

AC XY:

439225

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.687

Gnomad4 AMR exome

AF:

0.657

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.480

Gnomad4 SAS exome

AF:

0.526

Gnomad4 FIN exome

AF:

0.646

Gnomad4 NFE exome

AF:

0.616

Gnomad4 OTH exome

AF:

0.606

GnomAD4 genome

AF:

0.626

AC:

95225

AN:

152108

Hom.:

30064

Cov.:

AF XY:

0.627

AC XY:

46584

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.681

Gnomad4 AMR

AF:

0.649

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.458

Gnomad4 SAS

AF:

0.520

Gnomad4 FIN

AF:

0.647

Gnomad4 NFE

AF:

0.611

Gnomad4 OTH

AF:

0.628

Alfa

AF:

0.606

Hom.:

36298

Bravo

AF:

0.628

Asia WGS

AF:

0.482

AC:

1680

AN:

3478

EpiCase

AF:

0.595

EpiControl

AF:

0.591

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

not specified

Benign:2

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 85% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -

Periodic fever-infantile enterocolitis-autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Familial cold autoinflammatory syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Periodic fever-infantile enterocolitis-autoinflammatory syndrome;C4015276:Familial cold autoinflammatory syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.41

DANN

Benign

0.30

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