rs148696946

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001199138.2(NLRC4):​c.90G>A​(p.Trp30*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

NLRC4
NM_001199138.2 stop_gained

Scores

2
2
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.688
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 2-32252591-C-T is Benign according to our data. Variant chr2-32252591-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 542043.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000164 (25/152330) while in subpopulation AFR AF= 0.000577 (24/41564). AF 95% confidence interval is 0.000398. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 25 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NLRC4NM_001199138.2 linkuse as main transcriptc.90G>A p.Trp30* stop_gained 3/9 ENST00000402280.6 NP_001186067.1 Q9NPP4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NLRC4ENST00000402280.6 linkuse as main transcriptc.90G>A p.Trp30* stop_gained 3/91 NM_001199138.2 ENSP00000385428.1 Q9NPP4-1

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152212
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000579
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000437
AC:
11
AN:
251468
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.000554
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461818
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.0000224
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152330
Hom.:
0
Cov.:
31
AF XY:
0.000215
AC XY:
16
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.000577
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000581
Hom.:
0
Bravo
AF:
0.000147
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Periodic fever-infantile enterocolitis-autoinflammatory syndrome;C4015276:Familial cold autoinflammatory syndrome 4 Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 09, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Pathogenic
0.39
CADD
Pathogenic
28
DANN
Uncertain
0.98
Eigen
Uncertain
0.41
Eigen_PC
Benign
0.11
FATHMM_MKL
Benign
0.043
N
Vest4
0.89
GERP RS
2.3

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.

Other links and lift over

dbSNP: rs148696946; hg19: chr2-32477660; API