Variant chr2-32238296-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001199138.2(NLRC4):c.2357G>A(p.Gly786Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,608,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G786V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NLRC4
NM_001199138.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24475387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC4	NM_001199138.2 linkuse as main transcript	c.2357G>A	p.Gly786Asp	missense_variant	6/9	ENST00000402280.6	NP_001186067.1	Q9NPP4-1
NLRC4	NM_001199139.1 linkuse as main transcript	c.2357G>A	p.Gly786Asp	missense_variant	6/9		NP_001186068.1	Q9NPP4-1
NLRC4	NM_021209.4 linkuse as main transcript	c.2357G>A	p.Gly786Asp	missense_variant	6/9		NP_067032.3	Q9NPP4-1
NLRC4	NM_001302504.1 linkuse as main transcript	c.362G>A	p.Gly121Asp	missense_variant	5/8		NP_001289433.1	Q9NPP4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRC4	ENST00000402280.6 linkuse as main transcript	c.2357G>A	p.Gly786Asp	missense_variant	6/9	1	NM_001199138.2	ENSP00000385428.1		Q9NPP4-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724420

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.090

DEOGEN2

Benign

0.35

T;T;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.77

.;.;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.9

L;L;.;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.25

T;T;T;T

Polyphen

0.59

P;P;B;P

Vest4

0.66

MutPred

0.51

Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);.;Gain of relative solvent accessibility (P = 0.09);

MVP

0.44

MPC

0.28

ClinPred

0.47

GERP RS

2.8

Varity_R

0.063

gMVP

0.65

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over