rs11653414

chr17-5511718-A-C

Variant summary

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

The ENST00000574512.1(NLRP1):n.821-5741T>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 0.165 in 142,906 control chromosomes in the GnomAD database, including 3,623 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 0.17 (3623 hom., cov: 31)
• Consequence: NLRP1 ENST00000574512.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.42

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=-1.09).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRP1	NM_001033053.3	c.4069+6028T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRP1	ENST00000574512.1	n.821-5741T>G		intron_variant, non_coding_transcript_variant		1
NLRP1	ENST00000262467.11	c.4069+6028T>G		intron_variant		5
NLRP1	ENST00000699613.1	c.4102+3755T>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.165 AC: 23545 AN: 142808 Hom.: 3605 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.0302

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0826

Gnomad EAS AF: 0.0784

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.165 AC: 23602 AN: 142906 Hom.: 3623 Cov.: 31 AF XY: 0.161 AC XY: 11149 AN XY: 69110

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0826

Gnomad4 EAS AF: 0.0784

Gnomad4 SAS AF: 0.0393

Gnomad4 FIN AF: 0.0452

Gnomad4 NFE AF: 0.0599

Gnomad4 OTH AF: 0.157

Alfa AF: 0.117 Hom.: 387

Bravo AF: 0.173

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.43
Dann	Benign	0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11653414; hg19: chr17-5415038;