chr19-55971826-C-T

Variant names:

• chr19-55971826-C-T
• rs306487
• ENST00000291971.7:c.2534+1130C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000291971.7(NLRP8):​c.2534+1130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,000 control chromosomes in the GnomAD database, including 39,274 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 0.72 (39274 hom., cov: 31)
• Consequence: NLRP8 ENST00000291971.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000291971.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP8	NM_001433706.1		c.2534+1130C>T		intron	N/A	NP_001420635.1
	NLRP8	NM_001317000.1		c.2534+1130C>T		intron	N/A	NP_001303929.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP8	ENST00000291971.7	TSL:1 MANE Select	c.2534+1130C>T		intron	N/A	ENSP00000291971.3
	NLRP8	ENST00000590542.1	TSL:1	c.2534+1130C>T		intron	N/A	ENSP00000468121.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109142 AN: 151882 Hom.: 39257 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.718 AC: 109209 AN: 152000 Hom.: 39274 Cov.: 31 AF XY: 0.719 AC XY: 53412 AN XY: 74260

African (AFR) AF: 0.760 AC: 31507 AN: 41450

American (AMR) AF: 0.679 AC: 10374 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2620 AN: 3468

East Asian (EAS) AF: 0.821 AC: 4240 AN: 5166

South Asian (SAS) AF: 0.757 AC: 3652 AN: 4822

European-Finnish (FIN) AF: 0.745 AC: 7859 AN: 10556

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46552 AN: 67956

Other (OTH) AF: 0.727 AC: 1532 AN: 2108

Alfa AF: 0.689 Hom.: 57750

Bravo AF: 0.713

Asia WGS AF: 0.754 AC: 2618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.33
PhyloP100		-0.030
Mutation Taster		=100/0	polymorphism (auto)

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: rs306487; hg19: chr19-56483192;