chr19-55986594-C-A

Position:

• chr19-55986594-C-A

Variant summary

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

The NM_176811.2(NLRP8):​c.3048-1220C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,034 control chromosomes in the GnomAD database, including 10,642 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 0.37 (10642 hom., cov: 33)
• Consequence: NLRP8 NM_176811.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

Genes affected

NLRP8 (HGNC:22940): (NLR family pyrin domain containing 8) This gene encodes a member of the nucleotide-binding oligomerization domain/ leucine rich repeat/ pyrin domain containing (NLRP) subfamily, which belongs to the Nod-like receptor family of proteins. NLRP genes play roles in the mammalian innate immune system through inflammasome formation and activation of caspases. In addition, NLRP genes have been found to function during mammalian reproduction. Consistent with a function during human preimplantation development, this gene is expressed at high levels in oocytes with decreased levels in embryos. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP8	NM_176811.2	c.3048-1220C>A		intron_variant		ENST00000291971.7	NP_789781.2
NLRP8	NM_001317000.1	c.2991-1220C>A		intron_variant			NP_001303929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP8	ENST00000291971.7	c.3048-1220C>A		intron_variant		1	NM_176811.2	ENSP00000291971.3
NLRP8	ENST00000590542.1	c.2991-1220C>A		intron_variant		1		ENSP00000468121.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56249 AN: 151916 Hom.: 10627 Cov.: 33

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.370 AC: 56312 AN: 152034 Hom.: 10642 Cov.: 33 AF XY: 0.373 AC XY: 27726 AN XY: 74306

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.337

Alfa AF: 0.358 Hom.: 11592

Bravo AF: 0.361

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16986856; hg19: chr19-56497960;