rs9889625

chr17-5543296-G-Achr17-5543296-G-C

Variant summary

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

The NM_033004.4(NLRP1):c.2529-1269C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,146 control chromosomes in the GnomAD database, including 7,983 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 0.29 (7983 hom., cov: 31)
• Consequence: NLRP1 NM_033004.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP1	NM_033004.4	c.2529-1269C>T		intron_variant		ENST00000572272.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP1	ENST00000572272.6	c.2529-1269C>T		intron_variant		1	NM_033004.4	P2

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43572 AN: 152028 Hom.: 7982 Cov.: 31

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.286 AC: 43583 AN: 152146 Hom.: 7983 Cov.: 31 AF XY: 0.288 AC XY: 21401 AN XY: 74372

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.0245

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.285

Alfa AF: 0.245 Hom.: 869

Bravo AF: 0.272

Asia WGS AF: 0.131 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	5.1
Dann	Benign	0.65

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: rs9889625; hg19: chr17-5446616;