NM_176811.2:c.3048-1220C>A

Variant names:

• chr19-55986594-C-A
• rs16986856
• ENST00000291971.7:c.3048-1220C>A

Variant summary

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

The ENST00000291971.7(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 ENST00000291971.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 6 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]

NLRP5 (HGNC:21269): (NLR family pyrin domain containing 5) The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). Expression of this gene is restricted to the oocyte. A mouse gene that encodes a maternal oocyte protein, similar to this encoded protein, is required for normal early embryogenesis. [provided by RefSeq, Jul 2008]

NLRP5 Gene-Disease associations (from GenCC):

• oocyte/zygote/embryo maturation arrest 19

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP8	NM_001317000.1		c.2991-1220C>A		intron	N/A	NP_001303929.1	Q86W28-2
	NLRP5	NM_001433705.1		c.-299C>A		upstream_gene	N/A	NP_001420634.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP8	ENST00000291971.7	TSL:1 MANE Select	c.3048-1220C>A		intron	N/A	ENSP00000291971.3	Q86W28-1
	NLRP8	ENST00000590542.1	TSL:1	c.2991-1220C>A		intron	N/A	ENSP00000468121.1	Q86W28-2
	NLRP5	ENST00000850973.1		c.-299C>A		upstream_gene	N/A	ENSP00000521055.1

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

African (AFR) AF: 0.381 AC: 15815 AN: 41466

American (AMR) AF: 0.394 AC: 6023 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3472

East Asian (EAS) AF: 0.130 AC: 672 AN: 5178

South Asian (SAS) AF: 0.342 AC: 1648 AN: 4812

European-Finnish (FIN) AF: 0.477 AC: 5036 AN: 10552

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24797 AN: 67964

Other (OTH) AF: 0.337 AC: 712 AN: 2112

Alfa AF: 0.361 Hom.: 35406

Bravo AF: 0.361

Asia WGS AF: 0.255 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.85
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16986856; hg19: chr19-56497960;