17-5584828-C-T

Variant names:

• chr17-5584828-C-T
• rs925597
• ENST00000576905.6:c.-354-328G>A

Variant summary

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

The ENST00000576905.6(NLRP1):​c.-354-328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,048 control chromosomes in the GnomAD database, including 15,627 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 0.45 (15627 hom., cov: 33)
• Consequence: NLRP1 ENST00000576905.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP1	ENST00000576905.6	c.-354-328G>A		intron_variant	Intron 1 of 17	4		ENSP00000458303.2
NLRP1	ENST00000572143.2	n.-543-328G>A		intron_variant	Intron 1 of 17	4		ENSP00000514476.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68251 AN: 151932 Hom.: 15604 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.449 AC: 68328 AN: 152048 Hom.: 15627 Cov.: 33 AF XY: 0.448 AC XY: 33310 AN XY: 74326

African (AFR) AF: 0.437 AC: 18119 AN: 41490

American (AMR) AF: 0.457 AC: 6973 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1637 AN: 3472

East Asian (EAS) AF: 0.182 AC: 938 AN: 5162

South Asian (SAS) AF: 0.407 AC: 1961 AN: 4816

European-Finnish (FIN) AF: 0.457 AC: 4834 AN: 10574

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32273 AN: 67950

Other (OTH) AF: 0.446 AC: 942 AN: 2114

Alfa AF: 0.455 Hom.: 2009

Bravo AF: 0.447

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.89
PhyloP100		-0.52
PromoterAI		0.13	Neutral

Splicing

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

Publications

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Other links and lift over

dbSNP: rs925597; hg19: chr17-5488148;