19-55869766-A-G

Position:

• chr19-55869766-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134444.5(NLRP4):​c.2355-1061A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,184 control chromosomes in the GnomAD database, including 34,519 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34519 hom., cov: 28)
• Consequence: NLRP4 NM_134444.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP4	NM_134444.5	c.2355-1061A>G		intron_variant		ENST00000301295.11	NP_604393.2
NLRP4	XM_017026344.1	c.2187-1061A>G		intron_variant			XP_016881833.1
NLRP4	XM_017026345.1	c.2355-1061A>G		intron_variant			XP_016881834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP4	ENST00000301295.11	c.2355-1061A>G		intron_variant		1	NM_134444.5	ENSP00000301295.4
NLRP4	ENST00000589437.1	c.882-1061A>G		intron_variant		1		ENSP00000468754.1
NLRP4	ENST00000587891.5	c.2130-1061A>G		intron_variant		2		ENSP00000465463.1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101422 AN: 151066 Hom.: 34477 Cov.: 28

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.713

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.671 AC: 101520 AN: 151184 Hom.: 34519 Cov.: 28 AF XY: 0.666 AC XY: 49160 AN XY: 73794

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.712

Alfa AF: 0.683 Hom.: 72000

Bravo AF: 0.696

Asia WGS AF: 0.695 AC: 2415 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.45

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: rs302437; hg19: chr19-56381132;