19-55857839-G-GA

Position:

• chr19-55857839-G-GA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_134444.5(NLRP4):​c.446_447insA​(p.Thr150fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NLRP4 NM_134444.5 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.31

Genes affected

NLRP4 (HGNC:22943): (NLR family pyrin domain containing 4) The protein encoded by this gene is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family, and is predicted to contain an N-terminal pyrin effector domain (PYD), a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). This gene product has a demonstrated role as a negative regulator of autophagy and type I interferon signaling pathways as a result of protein interactions with its NACHT domain. The PYD domain has also been shown to be important in the inhibition of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells). [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP4	NM_134444.5	c.446_447insA	p.Thr150fs	frameshift_variant	3/10	ENST00000301295.11	NP_604393.2
NLRP4	XM_017026344.1	c.446_447insA	p.Thr150fs	frameshift_variant	2/8		XP_016881833.1
NLRP4	XM_017026345.1	c.446_447insA	p.Thr150fs	frameshift_variant	2/8		XP_016881834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP4	ENST00000301295.11	c.446_447insA	p.Thr150fs	frameshift_variant	3/10	1	NM_134444.5	ENSP00000301295.4
NLRP4	ENST00000587891.5	c.221_222insA	p.Thr75fs	frameshift_variant	1/8	2		ENSP00000465463.1
NLRP4	ENST00000587464.1	c.446_447insA	p.Thr150fs	frameshift_variant	3/3	2		ENSP00000468496.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Human Evolutionary Genetics, Institut Pasteur

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs199475745; hg19: chr19-56369205;