rs3926687

Positions:

• chr17-5589116-G-A

Variant summary

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

The ENST00000576905.6(NLRP1):​c.-354-4616C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,142 control chromosomes in the GnomAD database, including 10,631 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 0.34 (10631 hom., cov: 32)
• Consequence: NLRP1 ENST00000576905.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830

Genes affected

NLRP1 (HGNC:14374): (NLR family pyrin domain containing 1) This gene encodes a member of the Ced-4 family of apoptosis proteins. Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The encoded protein contains a distinct N-terminal pyrin-like motif, which is possibly involved in protein-protein interactions. This protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to induce apoptosis in cells. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

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 (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP1	ENST00000576905.6	c.-354-4616C>T		intron_variant		4
NLRP1	ENST00000572143.2	c.-543-4616C>T		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52119 AN: 152024 Hom.: 10625 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.0298

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.343 AC: 52156 AN: 152142 Hom.: 10631 Cov.: 32 AF XY: 0.341 AC XY: 25351 AN XY: 74360

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.0299

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.359

Alfa AF: 0.430 Hom.: 18908

Bravo AF: 0.331

Asia WGS AF: 0.147 AC: 513 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	0.74
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3926687; hg19: chr17-5492436;