rs9900356

Positions:

• chr17-5515958-C-T

Variant summary

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

The ENST00000572272.6(NLRP1):​c.4058-441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,178 control chromosomes in the GnomAD database, including 52,224 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 0.83 (52224 hom., cov: 33)
• Consequence: NLRP1 ENST00000572272.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

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 (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP1	NM_033004.4	c.4058-441G>A		intron_variant		ENST00000572272.6	NP_127497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP1	ENST00000572272.6	c.4058-441G>A		intron_variant		1	NM_033004.4	ENSP00000460475	P2

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125671 AN: 152060 Hom.: 52175 Cov.: 33

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.827 AC: 125777 AN: 152178 Hom.: 52224 Cov.: 33 AF XY: 0.830 AC XY: 61744 AN XY: 74404

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.798

Alfa AF: 0.785 Hom.: 46837

Bravo AF: 0.823

Asia WGS AF: 0.868 AC: 3020 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	2.0
DANN	Benign	0.62

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: rs9900356; hg19: chr17-5419278;