rs379327

Variant names:

• chr19-55858800-C-A
• rs379327
• NM_134444.5:c.1407C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-55858800-C-A
• chr19-55858800-C-G
• chr19-55858800-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_134444.5(NLRP4):​c.1407C>A​(p.His469Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NLRP4 NM_134444.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23281959).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134444.5. 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
	NLRP4	NM_134444.5	MANE Select	c.1407C>A	p.His469Gln	missense	Exon 3 of 10	NP_604393.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP4	ENST00000301295.11	TSL:1 MANE Select	c.1407C>A	p.His469Gln	missense	Exon 3 of 10	ENSP00000301295.4
	NLRP4	ENST00000589437.1	TSL:1	c.102C>A	p.His34Gln	missense	Exon 1 of 7	ENSP00000468754.1
	NLRP4	ENST00000587891.5	TSL:2	c.1182C>A	p.His394Gln	missense	Exon 1 of 8	ENSP00000465463.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.87
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.4
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.29
Sift	Benign	0.29	T
Sift4G	Benign	0.25	T
Polyphen		0.99	D
Vest4		0.12
MutPred		0.36		Loss of catalytic residue at K467 (P = 0.0489)
MVP		0.81
MPC		0.095
ClinPred		0.29	T
GERP RS		0.63
PromoterAI		0.0028	Neutral
Varity_R		0.14
gMVP		0.048
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs379327; hg19: chr19-56370166;