rs8079727

chr17-5509153-A-Cchr17-5509153-A-T

Variant summary

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

The ENST00000574512.1(NLRP1):n.821-3176T>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,028 control chromosomes in the GnomAD database, including 7,850 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 0.31 (7850 hom., cov: 32)
• Consequence: NLRP1 ENST00000574512.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP1	NM_001033053.3	c.4070-7281T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP1	ENST00000574512.1	n.821-3176T>G		intron_variant, non_coding_transcript_variant		1
NLRP1	ENST00000262467.11	c.4070-7281T>G		intron_variant		5
NLRP1	ENST00000699613.1	c.4102+6320T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46551 AN: 151910 Hom.: 7810 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.307 AC: 46655 AN: 152028 Hom.: 7850 Cov.: 32 AF XY: 0.307 AC XY: 22801 AN XY: 74300

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.271

Alfa AF: 0.238 Hom.: 2462

Bravo AF: 0.305

Asia WGS AF: 0.336 AC: 1171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.64
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8079727; hg19: chr17-5412473; COSMIC: COSV52561847; COSMIC: COSV52561847;