NLRC4 p.Val416Val

Variant names:

• chr2-32250615-T-T
• NM_001199138.2:c.

Your query was ambiguous. Multiple possible variants found:

• chr2-32250616--
• chr2-32250616-C-A
• chr2-32250616-C-G
• chr2-32250616-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001199138.2(NLRC4):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NLRC4 NM_001199138.2 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• periodic fever-infantile enterocolitis-autoinflammatory syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Orphanet, Labcorp Genetics (formerly Invitae)
• familial cold autoinflammatory syndrome 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000289727 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199138.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRC4	NM_001199138.2	MANE Select	c.		exon_region	Exon 4 of 9	NP_001186067.1	Q9NPP4-1
	NLRC4	NM_001199139.1		c.		exon_region	Exon 4 of 9	NP_001186068.1	Q9NPP4-1
	NLRC4	NM_021209.4		c.		exon_region	Exon 4 of 9	NP_067032.3	Q9NPP4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRC4	ENST00000402280.6	TSL:1 MANE Select	c.		exon_region	Exon 4 of 9	ENSP00000385428.1	Q9NPP4-1
	NLRC4	ENST00000360906.9	TSL:1	c.		exon_region	Exon 4 of 9	ENSP00000354159.5	Q9NPP4-1
	NLRC4	ENST00000342905.10	TSL:1	c.		intron	N/A	ENSP00000339666.6	Q9NPP4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-32475684;